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Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice
Abstract
Background—: Altered composition of the gut microbiota is involved in both the onset and progression of obesity and diabetes mellitus. However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored. The present study was designed to investigate the role of Akkermansia muciniphila , a mucin-degrading bacterium with beneficial effects on metabolism, in the pathogenesis of atherosclerosis in apolipoprotein E–deficient ( Apoe −/− ) mice. Methods and Results—: Apoe −/− mice on normal chow diet or a Western diet were treated with A muciniphila by daily oral gavage for 8 weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time polymerase chain reaction analysis demonstrated that the fecal abundance of A muciniphila was significantly reduced by Western diet. Replenishment with A muciniphila reversed Western diet–induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia. A muciniphila prevented Western diet–induced inflammation in both the circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia. A muciniphila –mediated reduction in circulating endotoxin level could be attributed to the induction of intestinal expression of the tight junction proteins (zona occuldens protein-1 and occludin), thereby reversing Western diet–induced increases in gut permeability. Long-term infusion of endotoxin to Apoe −/− mice reversed the protective effect of A muciniphila against atherosclerosis. Conclusion—: A muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.
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TL;DR
In Apoe−/− mice, Western diet reduced gut *Akkermansia muciniphila* and exacerbated atherosclerosis; daily oral live *A. muciniphila* reduced lesion area and size by 31% and 48%, respectively, without changing hypercholesterolemia. The protection was linked to restored gut barrier, lower endotoxemia, and reduced local/systemic inflammation, and was reversed by long-term lipopolysaccharide infusion.
Key findings
- Western diet reduced fecal *A. muciniphila*; live *A. muciniphila* (5×10⁹ cfu daily) reduced Western diet-induced lesion area by 31% and lesion size by 48%, whereas heat-killed bacteria had no effect.
- *A. muciniphila* reduced macrophage infiltration and expression of ICAM-1, MCP-1, F4/80, and TNFα in lesions/aorta, and lowered circulating MCP-1, IL-1β, and sTNFR II; it did not affect adiponectin.
- *A. muciniphila* lowered lipopolysaccharide levels in mesenteric adipose tissue and serum, reduced gut permeability, increased ileal occludin and ZO-1, and partially restored inner mucin layer thickness.
- Long-term lipopolysaccharide infusion (250 µg/kg/day) restored serum lipopolysaccharide and reversed *A. muciniphila*’s protection against lesion area/size and inflammation.
Methods
- Eight-week-old male Apoe−/− mice were fed normal chow or Western diet for 8 weeks; Western diet groups received daily oral gavage of live *A. muciniphila* (5×10⁹ cfu in 200 µL PBS), heat-killed *A. muciniphila*, or PBS. A separate group received lipopolysaccharide via osmotic pumps at 250 µg/kg/day for the last 4 weeks.
- Lesion area/size were assessed by Oil Red O and hematoxylin and eosin staining with ImageJ; inflammation by immunofluorescence/immunohistochemistry and real-time PCR; gut permeability by FITC-dextran; lipopolysaccharide by LAL assay; Caco-2 cell experiments and denaturing gradient gel electrophoresis were also used.
- Sample sizes were n=8–10 for main groups and n=5–7 for lipopolysaccharide infusion groups; statistics used one-way ANOVA with Tukey or Games-Howell post hoc tests, Kruskal-Wallis, or unpaired t tests.
Limitations
- Stated: how gut-residing *A. muciniphila* increases tight junction protein expression remains to be determined.
- Evident: all experiments are in male Apoe−/− mice; no human clinical outcomes or human atherosclerosis endpoints are reported.
- Evident: the study tests one bacterial species under specific diets, with modest sample sizes (n=5–10 per group), and some mechanistic data are in online-only supplements.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These changes were accompanied by a marked attenuation in metabolic endotoxemia.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“muciniphila did not have a significant effect on either macrophage accumulation or expression of MCP-1, ICAM-1 and TNFα in the local aortic tissues (Figure 2A-2D and 3A-3D).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Ameliorated Both Aortic and Systemic Inflammation in Western Diet-Fed Apoe -/-Mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results showed that Western diet-induced aggravation of atherosclerotic lesion was accompanied by a marked reduction of A muciniphila”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lipopolysaccharide infusion also augmented the number of infiltrated macrophages and the expression of the inflammatory molecules MCP-1 and ICAM-1 in the atherosclerotic lesions of mice treated with A muciniphila (Figure 6A-6C).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Chronic Infusion of Lipopolysaccharide Abolished the Protective Effect of A muciniphila Against Western Diet-Induced Atherosclerosis in Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas restoration of A muciniphila by daily oral gavage substantially reduced atherosclerotic lesions in Apoe -/-mice.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, treatment with propionate or butyrate in Caco-2 cells failed to increase the expression of either occludin or ZO-1 (Figure IVC and IVD in the online-only Data Supplement).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the fecal amounts of this bacteria were comparable between wild-type and Apoe -/-mice fed a normal chow diet (7.31±0.51versus 7.04±0.69log10 bacteria/g feces in wild-type versus Apoe -/-)”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Oral Gavage With A muciniphila Protected Against Western Diet-Induced Atherosclerotic Lesion Formation in Apoe -/-Mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, this increased level of lipopolysaccharide was able to reverse the protective effect of A muciniphila treatment against atherosclerosis, as demonstrated by increased lesion area (Figure 5B and 5D) and size (Figure 5C and 5E) in Apoe -/-mice compared with the A muciniphila-treated mice without infusion of lipopolysaccharide.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Chronic Infusion of Lipopolysaccharide Abolished the Protective Effect of A muciniphila Against Western Diet-Induced Atherosclerosis in Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, treatment with A muciniphila inhibited the Western diet-induced protein expression of ICAM-1 and MCP-1”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Ameliorated Both Aortic and Systemic Inflammation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with the inoculating medium of A muciniphila culture (100 μL/mL) in Caco-2 cells, a human intestine epithelial cell line, significantly upregulated the expression of occludin and ZO-1 compared with those treated with the plain inoculating medium.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 36
- Probably not a substantial claim. 32
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Western diet-fed Apoe -/-mice showed a significant decrease in the inner mucin layer thickness of ileum, and A muciniphila treatment partially restored the thickness of this layer (Figure III in the online-only Data Supplement).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the daily oral gavage with A muciniphila did not affect the overall pattern of gut microbiota and abundance of the above-mentioned bacterial species (Figure IA-IF in the online-only Data Supplement).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Oral Gavage With A muciniphila Protected Against Western Diet-Induced Atherosclerotic Lesion Formation in Apoe -/-Mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the expression of the epithelial tight junction protein occludin was significantly reduced by Western diet feeding but was upregulated by treatment with live A muciniphila (Figure 4B, 4D, and 4F).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This pattern change was characterized by increased amounts of Proteobacteria and Firmicutes and a decreased quantity of Bacteroidetes, Fusobacteria, and Tenericutes (Figure IB-IF in the online-only Data Supplement)”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Oral Gavage With A muciniphila Protected Against Western Diet-Induced Atherosclerotic Lesion Formation in Apoe -/-Mice
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our atherogenic Apoe -/-model, there was no obvious change in food intake after A muciniphila treatment (Figure IG in the online-only Data Supplement), although there was a slight decrease in body weight and fat mass (Figure IH-IJ in the online-only Data Supplement).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Treatment With A muciniphila Did Not Alter Lipid Metabolism in Apoe -/-Mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The serum levels of these 2 proinflammatory factors were significantly increased in Western diet-fed Apoe -/- mice compared with the mice on normal chow diet, whereas these Western diet-induced elevations were obviously diminished by daily oral gavage with A muciniphila but not the heat-killed bacteria (Figure 3E and 3F).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Ameliorated Both Aortic and Systemic Inflammation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Western diet resulted in a 3.7fold increase in lesion area and a 2.9-fold increase in lesion size in Apoe -/-mice compared with normal chow diet (Figure 1D and 1E).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Oral Gavage With A muciniphila Protected Against Western Diet-Induced Atherosclerotic Lesion Formation in Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with A muciniphila substantially reduced the lesion area and size by 31% and 48%, respectively, in Apoe -/-mice fed a Western diet (Figure 1D and 1E).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Oral Gavage With A muciniphila Protected Against Western Diet-Induced Atherosclerotic Lesion Formation in Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A muciniphila prevented Western diet-induced inflammation in both the circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The in vivo gut permeability, as determined by oral administration of fluorescent labeled dextran (DX-4000-FITC) followed by measurement of its circulating concentration, was significantly higher in Western diet-fed Apoe -/-mice compared with the normal chow dietfed controls, whereas the Western diet-induced increase of gut permeability was largely blocked by the treatment with live A muciniphila”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In Apoe -/-mice on normal chow diet, treatment with A muciniphila has no obvious effect on gut permeability (Figure VA in the online-only Data Supplement), circulating levels of inflammatory markers (MCP-1, IL-1β, and sTNFR II; Figure VB-VD in the online-only Data Supplement), and atherosclerotic plaque formation (Figure VE and VF in the online-only Data Supplement)”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of macrophages in atherosclerotic lesions increased after Western diet feeding, and daily oral gavage with A muciniphila significantly reduced the amount, as shown by immunofluorescent staining of the macrophage marker monocytes/macrophages antigen (Figure 2A and 2D).”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Ameliorated Both Aortic and Systemic Inflammation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Replenishment with A muciniphila reversed Western diet-induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, A muciniphila had no effect on the Western diet-induced hypercholesterolemia and alterations in other metabolic profiles”
- Also stated in: § CLINICAL PERSPECTIVE · plain
“the daily oral gavage with A muciniphila did not alter serum levels of total cholesterol, total triglyceride, low-density lipoprotein, and high-density lipoprotein”
- Also stated in: § CLINICAL PERSPECTIVE · plain
“A muciniphila treatment did not significantly affect fasting blood glucose level or glucose tolerance in Apoe -/-mice”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § CLINICAL PERSPECTIVE · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present study demonstrates that the Western diet-induced deterioration of atherosclerosis in Apoe -/-mice is associated with an increased level of Firmicutes, a decreased amount of Bacteroidetes, and especially a marked reduction in A muciniphila in the gut.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“treatment with A muciniphila substantially reduced the expression of several chemokines and the adhesion molecules MCP-1, TNFα, and ICAM-1, along with lower aortic infiltration of macrophages and diminished atherosclerotic lesion in Apoe -/-mice.”
- Also stated in: § CLINICAL PERSPECTIVE · plain
“Local inflammation in aortic arch was reduced in Apoe -/-mice after oral gavage with Akkermansia muciniphila.”
- Also stated in: § CLINICAL PERSPECTIVE · plain
“Apoe -/-mice treated with Akkermansia muciniphila showed amelioration in both aortic expression and systemic levels of inflammatory molecules.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § CLINICAL PERSPECTIVE · plain
In the paper
“Bacterial DNA has been detected in atherosclerotic lesions, and the pyrosequencing result reveals that the bacteria in lesions are derived from gut and oral cavity, 13”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [13] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“supplementation with one of the species in this phylum, Faecalibacterium prausnitzii, improves the survival rate of chemical-induced colitis in animals.5”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [5] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Chlamydia pneumonia is present in atherosclerotic lesions of patients with previous exposure, and infection with this bacterium exacerbates atherosclerosis in animals.11,12”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [11]
- Not checked yetcites [12]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“supplementation with butyric acid improves the metabolic profiles in a dietary obese murine model.8”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [8]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“higher proportions of Firmicutes and lower levels of Bacteroidetes have been observed in obese individuals, and dietary intervention or bariatric surgery reverses these changes.6”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [6] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“A lower proportion of butyrate-producing bacteria have been found in individuals with autoimmune diabetes mellitus compared with healthy control subjects, 7”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [7]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Bacterial infection has been proposed as one of the triggers of inflammation in atherosclerosis.11,12”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [11]
- Not checked yetcites [12]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“decreased diversity within the phylum of Firmicutes in the gut microbiota is commonly found in patients with Crohn disease, 4”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [4]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Altered composition and function of gut microbiota have been linked to a number of chronic diseases, including colon cancer, irritated bowel syndrome, colitis, obesity, and diabetes mellitus.3”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [3] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Atherosclerosis, the main contributor to cardiovascular mortality, is a chronic inflammatory disease.10”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A smaller amount of A muciniphila in the gut has been observed in obese children and pregnant women.22,23”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [22] source
- Not checked yetcites [23]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“It accounts for ≈1% to 3% of the microbial community in healthy subjects, and its abundance is inversely correlated with body weight in mice and humans.20,21”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Akkermansia muciniphila, a mucin-degrading bacterium belonging to the generum of Verrucomicrobia, has recently emerged as an important component of the gut microbial ecosystem.19”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
What the sources say
- Not checked yetcites [19]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In mice fed a high-fat diet, A muciniphila given by daily oral gavage reverses fat mass gain, adipose tissue inflammation, and insulin resistance, 21,24”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“a metabolomics analysis shows that metabolism of dietary phosphatidylcholine by gut microbiota produces proatherogenic trimethylamine-N-oxide, which can accelerate atherosclerosis in mice.17,18”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the amount of intestinal A muciniphila under normal diet is sufficient to maintain the integrity of the gut barrier, thereby preventing endotoxinemiainduced systemic inflammation and atherosclerosis.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Gut permeability is regulated by the mucus layer and tight junctions of the intestine.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that A muciniphila blocked lipopolysaccharide penetration by preserving the gut barrier.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > A muciniphila Decreased Intestinal Permeability and Reduced the Penetration of Gut-Derived Lipopolysaccharide Into Circulation in Western Diet-Fed Apoe -/-Mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Gut permeability is regulated by the mucus layer and tight junctions of the intestine.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All the animal experiments were approved by the Committee on the Use of Live Animals for Teaching and Research of the University of Hong Kong.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Animal Model
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Metabolic endotoxemia, defined as a 2-to 3-fold elevation of the circulating endotoxin/lipopolysaccharide level, has been proposed as an initiating factor of obesity-related cardiometabolic dysfunction.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [9] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Bacterial DNA from the gut microbiota has been detected in human atherosclerotic plaques.13”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [13] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Inflammation and hypercholesterolemia are the 2 key etiological factors for atherosclerosis.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data are presented as mean±SEM; n=5 to 7.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“the primary control of the gut barrier relies on an intact epithelium where tight junctions sealing the space between individual epithelial cells maintain the epithelial integrity.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [50]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Loss of occludin leads to an increase in gut permeability, whereas deficiency of ZO-1 can interrupt the assembly of tight junction by inhibiting the recruitment of other components.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [50]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Notably, supplementation with prebiotics causes a >100-fold enrichment in gut A muciniphila.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [21] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings raise the possibility of targeting individual species of the gut microbiota for the treatment of atherosclerosis.”
- Also stated in: § Discussion · hedged
“suggesting that therapeutic interventions targeting this single genus/species in gut microbiota may represent a promising strategy for the treatment and prevention of both metabolic and cardiovascular disorders.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Data availability
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
- Also stated in: § Discussion · hedged
None of the sources cited for this claim have been checked yet.
In the paper
“Several recent studies have identified trimethylamine N-oxide, a metabolite of the gut microbiota, as an independent risk factor for cardiovascular disease.17,18,34”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that the antiatherogenic effect of A muciniphila is mediated by limiting the lipopolysaccharide level in the bloodstream and ameliorating metabolic endotoxemia.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Toll-like receptor 4 is expressed in various vascular cells, including endothelial cells, focal leukocytes, and macrophages.
- Rests on an assumption: Activation of Toll-like receptor 4 by lipopolysaccharide stimulates release of proinflammatory molecules from vascular cells and inhibits cholesterol efflux from macrophages, facilitating foam cell formation.
- Rests on an assumption: Lipopolysaccharide-induced inflammatory cytokines in perivascular adipose tissue can act in a paracrine manner to exacerbate vascular inflammation and atherosclerosis.
None of the sources cited for this claim have been checked yet.
In the paper
“A clinical study revealed that subclinical endotoxemia is a strong risk factor for carotid atherosclerosis and that weekly injection of lipopolysaccharide worsens the formation of atherosclerosis in animal models.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [41] source
- Not checked yetcites [42]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Western diet-induced atherosclerosis is caused partly by a reduction of A muciniphila in gut, resulting in compromised gut barrier and increased endotoxemia, which in turn exacerbate vascular inflammation.”
- Also stated in: § CLINICAL PERSPECTIVE · plain
“The antiatherogenic effect of A muciniphila was attributed to its ability to reduce aortic and systemic inflammation by protecting the integrity of gut barrier, thereby leading to alleviation of endotoxemia.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Data availability
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Toll-like receptor 4 is expressed in various vascular cells, including endothelial cells, focal leukocytes, and macrophages.
- Rests on an assumption: Activation of Toll-like receptor 4 by lipopolysaccharide stimulates release of proinflammatory molecules from vascular cells and inhibits cholesterol efflux from macrophages, facilitating foam cell formation.
- Rests on an assumption: Lipopolysaccharide-induced inflammatory cytokines in perivascular adipose tissue can act in a paracrine manner to exacerbate vascular inflammation and atherosclerosis.
- Rests on an assumption: Whether altered gut microbiota contributes to the pathogenesis of atherosclerosis remains unknown.
- Rests on an assumption: Hypercholesterolemia and chronic inflammation are the 2 important risk factors for atherosclerosis, which is a major cause of fatal cardiovascular complications.
- Rests on an assumption: Although cholesterol-lowering drugs can effectively reduce the incidence of atherosclerosis, anti-inflammatory therapies against this disease have had limited success, partly because of the lack of understanding of etiological factors that trigger vascular inflammation.
- Rests on an assumption: Previous clinical studies have reported a close association of bacterial infection and endotoxemia with cardiovascular diseases.
- Also stated in: § CLINICAL PERSPECTIVE · plain
In the paper
“lower diversity and abundance of gut microbiota is associated with certain diseases.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [35]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Notably, all these models showed a reduction of lesion area and lesional lipid content without any significant alteration of plasma cholesterol levels, which is similar to our findings of A muciniphila treatment.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [46]
- Not checked yetcites [47]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Current therapeutic options for treating or preventing atherosclerosis include mainly platelet aggregation inhibitors, statins, antihypertensives, and thrombolytic agents.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [40]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In obesity, inflammatory factors in adipose tissue are the major contributors to systemic inflammation.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [45]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“A positive correlation between serum lipopolysaccharide-binding protein level and carotid intima thickness and an association of Toll-like receptor 4 polymorphisms with decreased atherosclerosis have been found in humans.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [43]
- Not checked yetcites [44]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In the initial stage of atherosclerosis, injured or inflamed endothelium secretes adhesion molecules and chemokines to facilitate the recruitment and transmigration of leukocytes into the intima.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [10] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“However, the risks for fatal cardiovascular complications in these patients remain high because of the unsolved inflammation.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The mucus layer is enriched with various mucins that form a hydrated gel layer covering the mucosal surface to prevent adhesion of harmful bacteria.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [49]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Animal-based studies have reported the effectiveness of several anti-inflammatory interventions in alleviating atherosclerosis, including the CD40-TNF receptor-associated factor 6-specific blockade and IL-1 neutralization, but clinical implications of these findings remain to be confirmed.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [39] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The unresolved inflammation stimulates the expression of macrophage scavenger receptors and promotes the uptake of modified lipoproteins forming lipid-laden macrophages, which drives the inflammatory loop for further migration and proliferation of leukocytes and smooth muscle cells in the lesion area.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“A prebiotics-induced hypocholesterolemic effect has been reported in animals, suggesting a possible role in combating atherosclerosis.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [36]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Tight junction is a multiple protein complex including occludin, claudins, and ZOs.”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Discussion
What the sources say
- Not checked yetcites [50]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The link between gut microbiota and obesity-related cardiovascular complications has not been explored.
“However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored.”
The paper relies on this without support.
Direct evidence for the causative role of altered gut microbiota (dysbiosis) in the pathogenesis of atherosclerosis is still lacking.
“However, direct evidence for the causative role of altered gut microbiota (dysbiosis) in the pathogenesis of atherosclerosis is still lacking.”
The paper relies on this without support.
The beneficial role of A. muciniphila against obesity-related cardiovascular diseases remains to be addressed.
“However, its beneficial role against obesity-related cardiovascular diseases remains to be addressed.”
The paper relies on this without support.
Gut permeability is regulated by the mucus layer and tight junctions of the intestine.
“Gut permeability is regulated by the mucus layer and tight junctions of intestine.”
The paper relies on this without support.
Toll-like receptor 4 is expressed in various vascular cells, including endothelial cells, focal leukocytes, and macrophages.
“Toll-like receptor 4 is expressed in various vascular cells, including endothelial cells, focal leukocytes, and macrophages.”
The paper relies on this without support.
Activation of Toll-like receptor 4 by lipopolysaccharide stimulates release of proinflammatory molecules from vascular cells and inhibits cholesterol efflux from macrophages, facilitating foam cell formation.
“Its activation by lipopolysaccharide not only stimulates the release of proinflammatory molecules from these cells but also inhibits cholesterol efflux from macrophages and thus facilitates foam cell formation.”
The paper relies on this without support.
Lipopolysaccharide-induced inflammatory cytokines in perivascular adipose tissue can act in a paracrine manner to exacerbate vascular inflammation and atherosclerosis.
“Furthermore, lipopolysaccharide-induced inflammatory cytokines in perivascular adipose tissue, which surrounds almost all the blood vessels, can act in a paracrine manner to exacerbate vascular inflammation and atherosclerosis.”
The paper relies on this without support.
Whether altered gut microbiota contributes to the pathogenesis of atherosclerosis remains unknown.
“However, whether altered gut microbiota contributes to the pathogenesis of atherosclerosis remains unknown.”
The paper relies on this without support.
Hypercholesterolemia and chronic inflammation are the 2 important risk factors for atherosclerosis, which is a major cause of fatal cardiovascular complications.
“Hypercholesterolemia and chronic inflammation are the 2 important risk factors for atherosclerosis, which is a major cause of fatal cardiovascular complications, including coronary heart disease and myocardial infarction.”
The paper relies on this without support.
Although cholesterol-lowering drugs can effectively reduce the incidence of atherosclerosis, anti-inflammatory therapies against this disease have had limited success, partly because of the lack of understanding of etiological factors that trigger vascular inflammation.
“Although cholesterollowering drugs can effectively reduce the incidence of atherosclerosis, anti-inflammatory therapies against this disease have had limited success, partly because of the lack of the understanding of etiological factors that trigger vascular inflammation.”
The paper relies on this without support.
Previous clinical studies have reported a close association of bacterial infection and endotoxemia with cardiovascular diseases.
“Previous clinical studies have reported a close association of bacterial infection and endotoxemia with cardiovascular diseases.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Indeed, in preclinical models, gavage of western diet–fed Apoe−/− mice with live Akkermansia muciniphila decreased intestinal permeability and lowered fecal and circulating LPS levels, which was associated with reduced aortic atherosclerosis independent of lipid metabolism28.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [28]
In the citing paper
“In another recent study, provision of Akkermansia muciniphila was associated with reduced aortic atherosclerosis in the hypercholesterolemic Apoe−/− mouse model28.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [28]
In the citing paper
“Endotoxemia is known to cause systemic inflammation leading to the disruption of innate and adaptive immunity and the development of atherosclerosis.[34][35][36]”
From Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting durations of A muciniphila treatment in the LPS experiment
MajorThe Results state that mice received daily A muciniphila for a total of 8 weeks, whereas the Figure 5 caption says it was given daily for 4 weeks before the subsequent 4-week infusion. This changes the treatment schedule for the experiment used to test the proposed mechanism.
“A muciniphila was orally gavaged daily to Apoe -/-mice for a total of 8 weeks, and during the last 4 weeks, either lipopolysaccharide (250 µg/kg body weight per day) or PBS (vehicle control) was infused long term”
“either PBS (WD+PBS) or A muciniphila was given orally to Apoe -/-mice daily for 4 weeks, followed by long-term infusion of LPS (250 μg•kg -1 •d -1 ; WD+Akk+LPS) or vehicle control (WB+Akk) for another 4 weeks.”
Diet description conflicts with the cited germ-free mouse study
MinorThe text describes the germ-free Apoe-deficient mice as having been fed a high-cholesterol diet, but the title of its cited reference 14 specifies a standard low-cholesterol diet.
“the germ-free atherogenic mice lacking apolipoprotein E (Apoe -/ ) mice, which are without the colonization of gut microbiota, show a worsening of atherosclerotic lesions after being fed a high-cholesterol diet compared with the conventionally raised mice”
“14. Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R, Schwarzer M, Tlaskalova-Hogenova H. Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet.”
Citations
Cites
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Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
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Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
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Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
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Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
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Intestinal mucosal barrier function in health and disease
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Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease
Andersen, V. C., Hansen, A. K., & Heitmann, B. L. (2017) · Nutrients · doi:10.3390/nu9030286 · Cited by 34
“Hence, in obese mice, an increase in number of Akkermansia muciniphila has been correlated with increased numbers of goblet cells [83].”
BackgroundInfluence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome
Xue, J., Allaband, C., Zhou, D., Poulsen, O., Martino, C., Jiang, L., Tripathi, A., Elijah, E. O., Dorrestein, P. C., Knight, R. D., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.663950 · Cited by 34
Lu, S., Xu, S., Chen, L., Deng, Y., & Feng, J. (2022) · Antioxidants · doi:10.3390/antiox11091806 · Cited by 34
Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment
Zhai, T., Wang, P., Hu, X., & Zheng, L. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3900835 · Cited by 34
“Akkermansia muciniphila Mice ↓ TNF-α, MCP-1, IL-1β, LPS, Atherosclerotic plaques Prevention [105, 106]”
Yadav, M., Kumar, T., Kanakan, A., Maurya, R., Pandey, R., & Chauhan, N. S. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.932795 · Cited by 31
“, 2022a), as well as protects against atherosclerosis by reducing gut permeability and preventing inflammation (Li et al., 2016).”
BackgroundGut microbiota, immunity, and bile acid metabolism: decoding metabolic disease interactions
Zhao, Q., Wu, J., Ding, Y., Pang, Y., & Jiang, C. (2023) · Life Metabolism · doi:10.1093/lifemeta/load032 · Cited by 31
Both gut microbiota and cytokines act to atherosclerosis in ApoE−/− mice
Liu, Q., Li, Y., Song, X. M., Wang, J., He, Z., Zhu, J., Chen, H., Yuan, J., Zhang, X., Jiang, H., et al. (2019) · Microbial Pathogenesis · doi:10.1016/j.micpath.2019.103827 · Cited by 32
Afroz, K. F., Reyes, N., Young, K., Parikh, K., Misra, V., & Alviña, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-87678-x · Cited by 32
“5a and Supplementary Figure 1b, n = 16 in all groups; F(3,60) = 90.”
BackgroundFrancesco, M. A. D., & Caruso, A. (2022) · Vaccines · doi:10.3390/vaccines10020244 · Cited by 33
“Another study [61] found a decrease in Akkermansia muciniphila in psoriatic patients; this species has a protective role against inflammation and is involved in the strengthening of the intestinal barrier [61,62].”
BackgroundChayanupatkul, M., Somanawat, K., Chuaypen, N., Klaikeaw, N., Wanpiyarat, N., Siriviriyakul, P., Tumwasorn, S., & Werawatganon, D. (2022) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-022-03643-9 · Cited by 32
“Akkermansia muciniphila has been shown to increase gut microbiota diversity through short chain fatty acid production and strengthen intestinal barrier function by increasing mucin layer thickness and tight junction protein expression [30, 31].”
BackgroundPrebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis
Ren, L., Ma, X., Wang, H., Li, R., Cui, J., Yan, P.-J., Wang, Y., Yu, X.-Y., Du, P., Yu, H., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.06.031 · Cited by 32
Hao, L., Zhong, W. H., Woo, J. J., Wei, X., Ma, H., Dong, H., Guo, W., Sun, X., Yue, R., Zhao, J., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000019 · Cited by 32
“muciniphila administration reduced cardiovascular disease[8] and obesity,[9] making A.”
BackgroundGuo, H., Shen, H., Wang, L., Luo, Z., Zhang, J., Zhang, H., Gao, T.-L., Han, Y., & Jiang, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114754 · Cited by 35
Yang, H.-T., Xiu, W., Liu, J., Yang, Y., Zhang, Y., Zheng, Y., Wu, T., Hou, X., Wu, C.-X., Ma, Y., et al. (2022) · ACS Omega · doi:10.1021/acsomega.1c02120 · Cited by 30
Bacterial extracellular vesicles in the initiation, progression and treatment of atherosclerosis
Lin, Y., Wang, J., Bu, F., Zhang, R., Wang, J., Wang, Y., Huang, M., Huang, Y., Zheng, L., Wang, Q., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2452229 · Cited by 33
“108 Chelakkot et al. have extended our understanding of the beneficial impact of A. muciniphila on the integrity of gut barrier.”
Han, X., Wang, Y., Zhang, P., Zhu, M., Li, L., Mao, X., Sha, X., & Li, L. (2021) · Pharmaceutical Biology · doi:10.1080/13880209.2021.1954667 · Cited by 32
“For example, Prevotella copri and Bacteroides vulgatus contribute to insulin resistance, while Akkermansia municiphila and Faecalibacterium prausnitzii increase insulin sensitivity (Li et al. 2016).”
BackgroundModulation of gut microbiota by foods and herbs to prevent cardiovascular diseases
Panyod, S., Wu, W.-K., Chen, C., Wu, M., Ho, C., & Sheen, L. (2021) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2021.09.006 · Cited by 32
Panyod, S., Wu, W., Peng, S.-Y., Tseng, Y.-J., Hsieh, Y.-C., Chen, R.-A., Huang, H., Chen, Y., Chuang, H.-L., Hsu, C., et al. (2023) · npj Science of Food · doi:10.1038/s41538-023-00196-0 · Cited by 32
Impact of the gut microbiome on atherosclerosis
Mao, Y., Kong, C., Zang, T., You, L., Wang, L., Shen, L. W., & Ge, J. (2024) · mLife · doi:10.1002/mlf2.12110 · Cited by 30
“Li et al. found that A. muciniphila prevented and controlled in fl ammation in atherosclerotic lesions by reducing in fi ltration of macrophages, levels of proin fl ammatory cytokines, levels of chemokines, and endotoxemia 69 .”
BackgroundDownregulation of G3BP2 reduces atherosclerotic lesions in ApoE mice
Li, T., Safitri, M., Zhang, K., Wang, Y., Huang, L., Zhu, Y. S., Daniel, R. A., Wu, L. J., Qiu, J., & Wang, G. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.08.003 · Cited by 29
Zhang, H., Wang, J., Shen, J., Chen, S., Yuan, H., Zhang, X., Liu, X., Yu, Y., Li, X., Gao, Z., et al. (2024) · iMeta · doi:10.1002/imt2.220 · Cited by 31
“…of dairy products, several strains of probiotics, including but not limited to Bifidobacterium animalis, Lactobacillus gasseri , and Lactiplantibacillus plantarum , have been evaluated for their efficacy in treating obesity, nonalcoholic liver diseases (NASH), and type 2 diabetes [24, 25].”
BackgroundRole of Akkermansia muciniphila in insulin resistance
Zeng, Z., Chen, M., Liu, Y., Zhou, Y., Liu, H., Wang, S., & Ji, Y. (2024) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16747 · Cited by 30
The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis
Lässiger-Herfurth, A., Pontarollo, G., Grill, A., & Reinhardt, C. (2019) · Microorganisms · doi:10.3390/microorganisms7120691 · Cited by 32
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Zhang, L., Wang, F., Wang, J., Wang, Y., & Fang, Y. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15173 · Cited by 29
RetractedPedersen, K. B., Pulliam, C. F., Patel, A., Piero, F. D., Watanabe, T. T. N., Wankhade, U. D., Shankar, K., Hicks, C., & Ronis, M. J. J. (2018) · Carcinogenesis · doi:10.1093/carcin/bgy141 · Cited by 28
Arakawa, K., Ishigami, T., Nakai-Sugiyama, M., Chen, L., Doi, H., Kino, T., Minegishi, S., Saigoh-Teranaka, S., Nakashima-Sasaki, R., Hibi, K., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0218096 · Cited by 28
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Khalili, L., Centner, A. M., & Salazar, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043084 · Cited by 30
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Ding, Q., Tian, J., Li, M., Lian, F., Zhao, L., Wei, X., Han, L., Zheng, Y., Gao, Z., Yang, H., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.530160 · Cited by 28
“A. muciniphila has been shown to improve metabolic outcomes, including vascular function (Qin et al., 2012; Li et al., 2016), while participating in the protection of the intestinal mucosal barrier and controlling low-grade inflammation (Chelakkot et al., 2018; Lee et al., 2019; Tang et al., 2019).”
BackgroundMicrobiota-Mediated Immune Regulation in Atherosclerosis
Eshghjoo, S., Jayaraman, A., Sun, Y., & Alaniz, R. C. (2021) · Molecules · doi:10.3390/molecules26010179 · Cited by 29
“, insulin resistance (IR), type 2 diabetes, and atherosclerosis [77].”
BackgroundTwo Gut Microbiota-Derived Toxins Are Closely Associated with Cardiovascular Diseases: A Review
Yamashita, T., Yoshida, N., Emoto, T., Saito, Y., & Hirata, K. (2021) · Toxins · doi:10.3390/toxins13050297 · Cited by 26
“Increased gut permeability enhances the penetration of gut microbiotaderived LPS from the intestine into the bloodstream [11].”
Modifying the Microbiome as a Potential Mechanism of Photobiomodulation: A Case Report
Bicknell, B. T., Laakso, E., Liebert, A. D., & Kiat, H. (2021) · Photobiomodulation Photomedicine and Laser Surgery · doi:10.1089/photob.2021.0057 · Cited by 27
“12 16 Akkermansia has been shown to improve glucose tolerance, improve the intestinal barrier, and reduce elevated blood lipids in a mouse model of Alzheimer’s disease (AD) 17 and to promote weight loss and reduce liver dysfunction, cholesterol, and inflammatory markers in humans.”
Hamazaki, M., Sawada, T., Yamamura, T., Maeda, K., Mizutani, Y., Ishikawa, E., Furune, S., Yamamoto, K., Ishikawa, T., Kakushima, N., et al. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02408-5 · Cited by 27
Xiang, Z., Wu, J., Li, J., Zheng, S., Wei, X., & Xu, X. (2023) · Engineering · doi:10.1016/j.eng.2022.12.012 · Cited by 27
Self-citationFrom anaerobes to aerointolerant prokaryotes
Ndongo, S., Khelaifia, S., Lagier, J., & Raoult, D. (2019) · Human Microbiome Journal · doi:10.1016/j.humic.2019.100068 · Cited by 28
Trimethylamine N-oxide—a marker for atherosclerotic vascular disease
Xie, G., An, Y., Lin, P., Wang, Y., & Guo, L. (2021) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2203085 · Cited by 27
“Akkermansia muciniphila plays a protective role by improving intestinal barrier function to resist atherosclerosis [123].”
BackgroundGut Microbiome and Serum Metabolome Profiles of Capsaicin with Cognitive Benefits in APP/PS1 Mice
Li, J., Liao, X., Yin, X., Deng, Z., Hu, G., Zhang, W., Jiang, F., & Zhao, L. (2022) · Nutrients · doi:10.3390/nu15010118 · Cited by 26
Self-citationZhang, Z., Shi, X., Ji, J., Guo, Y., Peng, Q., Hao, L., Xue, Y., Liu, Y.-W., Li, C., Lu, J., et al. (2023) · Frontiers of Medicine · doi:10.1007/s11684-022-0978-2 · Cited by 28
“Our previous study showed that DHA inhibited YAP1 expression in liver tumor cells in vivo [23,24] and increased the abundance of A.”
BackgroundMethodInfluentialMachado, D., Almeida, D., Seabra, C. L., Andrade, J. C., Gomes, A., & Freitas, A. C. (2019) · Anaerobe · doi:10.1016/j.anaerobe.2019.102135 · Cited by 26
Characterization and Preliminary Safety Evaluation of Akkermansia muciniphila PROBIO
Ma, X., Tian, M., Yu, X., Liu, M., Li, B., Ren, D., & Wang, W. (2024) · Foods · doi:10.3390/foods13030442 · Cited by 25
“. acknowledged the including obesity [35,36], diabetes [37], hepatic steatosis [38], inflammation [15], and the efficacy of immunotherapy [39].”
BackgroundGinsenosides retard atherogenesis via remodelling host–microbiome metabolic homeostasis
Wang, Y., Wu, J., Hong, Y., Zhu, J., Zhang, Y., Zhang, J., Ding, C., Che, Y., Wang, G., Jiang, A., et al. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16320 · Cited by 29
Mei, L., Wang, J., Hao, Y., Zeng, X., Yang, Y., Wu, Z., & Ji, Y. S. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2416481 · Cited by 26
“…A. muciniphila enhances the integrity of the intestinal epithelial barrier, stimulates tight junction protein expression, and mitigates the rise in plasma endotoxins levels caused by increased intestinal permeability (Ashrafian et al. 2019a; Li et al. 2016; Reunanen et al. 2015; Shi et al. 2022).”
Anwardeen, N. R., Naja, K., & Elrayess, M. A. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1506767 · Cited by 29
Youssef, M., Ahmed, H. Y., Zongo, A. W., Korin, A., Zhan, F., Hady, E., Umair, M., Rajoka, M. S. R., Xiong, Y., & Li, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011290 · Cited by 30
“In addition, Akkermansia muciniphila effectively inhibited atherosclerotic injury in the Apoe−/− mice by improving TJ proteins’ expression associated with recovering the gut barrier and decreasing the formation of endotoxins-induced inflammation [78].”
BackgroundShirouchi, B., Fukuda, A., & Akasaka, T. (2022) · Metabolites · doi:10.3390/metabo12010064 · Cited by 25
“A previous study into ApoE−/− mice showed that the oral supplementation of Akkermansia muciniphila attenuated atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation by restoring the gut barrier function [21].”
BackgroundA Bibliometric Analysis of Research on the Links Between Gut Microbiota and Atherosclerosis
Wang, Y., Li, D., Jia, Z., Hui, J., Xin, Q., Zhou, Q., Cong, W., & Xu, F. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.941607 · Cited by 25
Kostiuchenko, O., Kravchenko, N., Markus, J., Burleigh, S., Fedkiv, O., Cao, L., Letašiová, S., Skibo, G. G., Hållenius, F. F., & Prykhodko, O. (2022) · Metabolites · doi:10.3390/metabo12111027 · Cited by 28
Bacterial Atlas of Mouse Gut Microbiota
Chu, M., & Zhang, X. (2022) · Cellular Microbiology · doi:10.1155/2022/5968814 · Cited by 24
Wu, X., Yu, D., Ma, Y., Fang, X., & Sun, P. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.142442 · Cited by 30
Chen, L., Ishigami, T., Doi, H., Arakawa, K., & Tamura, K. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01936-5 · Cited by 24
Labarta-Bajo, L., Gramalla-Schmitz, A., Gerner, R. R., Kazane, K. R., Humphrey, G., Schwartz, T., Sanders, K., Swafford, A. D.-E., Knight, R. D., Raffatellu, M., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003656117 · Cited by 26
Dubiński, P., Czarzasta, K., & Cudnoch‐Jędrzejewska, A. (2021) · Current Hypertension Reports · doi:10.1007/s11906-021-01144-7 · Cited by 27
Acharya, K. D., Noh, H. L., Graham, M. E., Suk, S., Friedline, R. H., Gomez, C. C., Parakoyi, A. E. R., Chen, J., Kim, J. K., & Tetel, M. J. (2021) · Metabolites · doi:10.3390/metabo11080499 · Cited by 22
“The specificities of occludin and ZO-1 on mouse intestinal tissue have been verified previously [74,108].”
BackgroundMorrison, M. C., Gart, E., van Duyvenvoorde, W., Snabel, J. M., Nielsen, M. J., Leeming, D. J., Menke, A. L., & Kleemann, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042325 · Cited by 23
“muciniphila (indicated by reduced plasma endotoxemia in mice [12,13,38] as well as humans [39]), we observed a reduction in gut permeability in an established functional gut permeability test (used in mice and humans) that measures the ability of the relatively impermeant FITC-labeled dextran (4 kDA) to cross from the…”
BackgroundBarbosa, J. C., Almeida, D., Machado, D., Sousa, S. C., Freitas, A. C., Andrade, J. C., & Gomes, A. (2022) · Pharmaceuticals · doi:10.3390/ph15050628 · Cited by 24
Lee, J., Kim, K. S., Koh, H., Lee, D.-W., & Kang, N. J. (2022) · Current Developments in Nutrition · doi:10.1093/cdn/nzac110 · Cited by 26
“muciniphila is a mucin-degrading bacterium (68), it decreases intestinal permeability by increasing the thickness of the mucin layer (69) and increases intestinal TJ protein expression and goblet cell den-”
BackgroundPuttarat, N., Kasorn, A., Vitheejongjaroen, P., Chantarangkul, C., Tangwattanachuleeporn, M., & Taweechotipatr, M. (2023) · Nutrients · doi:10.3390/nu15122710 · Cited by 25
“Akkermansia can inhibit atherosclerotic lesion formation and decrease circulating endotoxin levels through prevention of metabolic endotoxemia-induced inflammation in circulation and local vascular lesions [37].”
BackgroundMoleón, J., González‐Correa, C., Robles‐Vera, I., Miñano, S., de la Visitación, N., Barranco, A. M., Martín‐Morales, N., O’Valle, F., Mayo-Martínez, L., Garcı́a, A., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2247053 · Cited by 26
“58 Recent publications that study female NZBWF1 mice have demonstrated that there is a broad arrange of factors playing a role in the onset of hypertension besides B-cell hyperactivity and auto-antibody synthesis, such as pro-inflammatory cytokines or oxidative stress.”
BackgroundDiez‐Echave, P., Vezza, T., Rodríguez‐Nogales, A., Hidalgo‐Garcia, L., Garrido‐Mesa, J., Ruiz‐Malagón, A. J., Molina‐Tijeras, J. A., Romero, M., Robles‐Vera, I., Leyva‐Jiménez, F. J., et al. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202000005 · Cited by 24
Ahmed, L. A., & Al‐Massri, K. F. (2022) · Current Molecular Pharmacology · doi:10.2174/1874467215666220222105004 · Cited by 23
Nie, H., Zhou, Y., Yu, X., Yin, C., Li, L., Hao, H.-Q., Tao, Y., & Pan, Y. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01238-3 · Cited by 23
“It is well established that intestinal permeability is controlled by several tight junction protein, such as zonula occludens (ZO)-1 and occludin [7, 8].”
InfluentialMa, X., Li, M., Zhang, Y., Xu, T., Zhou, X., Qian, M., Yang, Z., & Han, X. (2023) · eLife · doi:10.7554/elife.92906.5 · Cited by 43
Jena, P. K., Wakita, D., Gomez, A. C., de Carvalho, T. T., Atici, A. E., Aubuchon, E. A., Narayanan, M., Lee, Y., Fishbein, M. C., Takasato, Y., et al. (2025) · Circulation Research · doi:10.1161/circresaha.124.325079 · Cited by 25
“40,42,68,69 Our findings are in line with previous studies that reported decreased abundances of SCFA-producing bacteria in the feces of patients during the KD acute phase.”
Obesity: More Than an Inflammatory, an Infectious Disease?
Leocádio, P. C. L., Oriá, R. B., Lopez, M. E. C., & Alvarez-Leite, J. I. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03092 · Cited by 23
Implications of gut microbiome on coronary artery disease
Xu, J., & Yang, Y. (2020) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt-20-428 · Cited by 22
“Akkermansia muciniphila, a mucindegrading bacterium with beneficial effects on obesityrelated metabolic disorders, attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through the restoration of the gut barrier in ApoE mice (70).”
BackgroundYan, C., Zhang, C., Cao, X., Feng, B., & Li, X. (2020) · Molecules · doi:10.3390/molecules25245857 · Cited by 24
“Recent evidence has suggested that the abundance of Akkermansia muciniphila in mouse models is inversely associated with obesity [33], insulin resistance [34], hepatic steatosis [35], and atherosclerosis [36], among others.”
BackgroundRong, B., Wu, Q., Saeed, M., & Sun, C. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.09.009 · Cited by 24
“Hence, research regarding the relationships between gutmicrobiota and host physiology during IF has gradually become a hot point (Li et al., 2016; Zarrinpar et al., 2014).”
BackgroundAtheroprotective Effects and Molecular Mechanism of Berberine
Lü, X., Zhou, X., Li, A., Li, H.-J., He, C., Qin, W. D., Zhao, D., Li, P.-Q., Zhu, L., & Cao, H. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.762673 · Cited by 23
“In line with those findings, replenishment with Akkermansia significantly reduced atherosclerosis induced by a high-fat diet by attenuating the aortic and systemic metabolic inflammatory response (Li et al., 2016).”
ResultClassical methods and perspectives for manipulating the human gut microbial ecosystem
Avalos, J. A. J., Arrevillaga-Boni, G., González‐López, L., García-Carvajal, Z. Y., & González‐Ávila, M. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1724075 · Cited by 23
Nutrigenomics and microbiome shaping the future of personalized medicine: a review article
Kassem, N. M. A., Abdelmegid, Y. A., El-Sayed, M., Sayed, R. S., Abdel-Aalla, M. H., & Kassem, H. A. (2023) · Journal of Genetic Engineering and Biotechnology · doi:10.1186/s43141-023-00599-2 · Cited by 22
“On the other hand, microbiota can also protect from atherosclerosis, as it was established in a recent study that showed that Akkermansia municiphila reversed Western diet-induced atherosclerosis in mice [11].”
ResultMulti-omics integration reveals functional signatures of gut microbiome in atherosclerosis
Shi, H., Wu, M., Wu, X., Liu, Z., Jiang, S., Li, G., Yang, Y., Fu, Y., Wang, Q., Zhang, G., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2542384 · Cited by 22
“36 Our findings indicate that Ethanol may exert a protective effect on AS, which aligns with recent large-cohort epidemiological studies.”
Targeting the Gut Microbiota for Remediating Obesity and Related Metabolic Disorders
Wang, B., Wang, L., Wang, H., Dai, H., Lu, X., Lee, Y. K., Gu, Z., Zhao, J., Zhang, H., Chen, W., et al. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab103 · Cited by 26
Adithya, K. K., Rajeev, R., Selvin, J., & Kiran, G. S. (2021) · ACS Food Science & Technology · doi:10.1021/acsfoodscitech.0c00075 · Cited by 23
Nie, H., Xiong, Q., Lan, G., Song, C., Yu, X., Chen, L., Wang, D., Ren, T., Chen, Z., Liu, X., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.838688 · Cited by 22
Akkermansia muciniphila attenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway
Shi, J., Wang, F., Tang, L., Li, Z., Yu, M., Bai, Y., Weng, Z., Sheng, M., He, W., & Chen, Y. (2022) · FEMS Microbiology Letters · doi:10.1093/femsle/fnac103 · Cited by 22
Tu, T., Liu, H., Liu, Z., Liang, Y., Tan, C., Feng, D., & Zou, J. (2023) · Nutrition & Metabolism · doi:10.1186/s12986-023-00772-x · Cited by 24
“…with Akkermansia could stimulate the expression of intestinal tight junction proteins such as ZO-1 and occludin and reduce intestinal permeability and serum endotoxin levels, thereby alleviating endotoxin-induced inflammation and preventing atherosclerosis in ApoE − / − mice fed western diet [28].”
BackgroundResultMiao, G., Guo, J., Zhang, W., Lai, P., Xu, Y., Chen, J., Zhang, L., Zhou, Z., Han, Y., Chen, G., et al. (2024) · Research · doi:10.34133/research.0363 · Cited by 25
Ma, L., Gao, Y., Yang, G., Zhao, L., Zhao, Z., Zhao, Y., Zhang, Y., Li, S., & Li, S. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s451565 · Cited by 22
“35 At the phylum level, notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as Firmicutes and Proteobacteria ) and increasing the quantity of probiotic bacteria (such as Bacteroidetes ).”
BackgroundSurrogate markers of intestinal dysfunction associated with survival in advanced cancers
Birebent, R., Drubay, D., Alves Costa Silva, C., Marmorino, F., Vitali, G., Piccinno, G., Hurtado, Y., Bonato, A., Belluomini, L., Messaoudene, M., et al. (2025) · OncoImmunology · doi:10.1080/2162402x.2025.2484880 · Cited by 21
Wang, J., Shan, S., Lyu, A., Wan, Y., & Zhang, J. (2021) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x21500798 · Cited by 21
Zhao, L., Wang, S., Zhang, N., Zhou, J., Mehmood, A., Raka, R. N., Zhou, F. L., & Zhao, L. (2022) · Antioxidants · doi:10.3390/antiox11061211 · Cited by 23
Zhang, F., & Wang, D. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1191445 · Cited by 23
“muciniphila caused a damage to the tight junction (TJ) of the BBB and the intestinal barrier (Li et al., 2016).”
BackgroundYe, D., Miyoshi, A., Ushitani, T., Kadoya, M., Igeta, M., Konishi, K., Shoji, T., Yasuda, K., Kitaoka, S., Yagi, H., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.12.022 · Cited by 21
Etlin, S. M., Rose, J. K., Bielski, L., Walter, C. E., Kleinman, A. S., & Mason, C. E. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00163-22 · Cited by 26
Lamminpää, I., Amedei, A., & Parolini, C. (2024) · Marine Drugs · doi:10.3390/md22110523 · Cited by 21
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Gut microbiome sheds light on the development and treatment of abdominal aortic aneurysm
Ling, X., Jie, W., Qin, X., Zhang, S., Shi, K., Li, T., & Guo, J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1063683 · Cited by 24
“muciniphila, was found to be significantly reduced in AAA mice, and it was found to improve AS and repair the damaged gut barrier in ApoE(−/−) mice AS model (126).”
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Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection
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“Some studies have shown that the use of probiotics can reduce the risk of cardiovascular disease [41,42].”
BackgroundBacterial Postbiotics as Promising Tools to Mitigate Cardiometabolic Diseases
Anhê, F. F., Jensen, B. A. H., Perazza, L. R., Tchernof, A., Schertzer, J. D., & Marette, A. (2021) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2021.10.2.123 · Cited by 20
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“8,9,13,26,27 Our study provides novel insights into how live A. muciniphila Muc T influences mucin production and glycosylation.”
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The Role of Gut Microbiota in Host Lipid Metabolism: An Eye on Causation and Connection
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Metadata
- Authors
- Li, J., Lin, S., Vanhoutte, P. M., Woo, C. W., & Xu, A.
- Affiliations
- Jinan University (CN)
- Venue
- Circulation
- Published
- 2016-06-14
- Volume
- 133
- Issue
- 24
- Pages
- 2434-2446
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2344498019
- Semantic Scholar
- c6057c9cf032a166c2516e352216f0144b27de52
- Cited by
- 775
- References
- 50
- Citations by year
- 2026: 44 · 2025: 92 · 2024: 107 · 2023: 91 · 2022: 124 · 2021: 88 · 2020: 82 · 2019: 62 · 2018: 38 · 2017: 41 · 2016: 6
- FWCI
- 25.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- Akkermansia muciniphila, atherosclerosis, metabolic endotoxemia, gut microbiota, ApoE-deficient mice, Western diet, intestinal permeability, tight junction proteins, macrophage infiltration, inflammatory cytokines, chemokines, intestinal barrier, obesity-related cardiovascular disease, hypercholesterolemia
- MeSH terms
- Animals, Disease Models, Animal, Humans, Inflammation, Intestines, Male, Mice, Transgenic, Treatment Outcome, Caco-2 Cells, Endotoxemia, Atherosclerosis, Mice, Verrucomicrobia
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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