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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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Reduction of aGVHD using chicken antibodies directed against intestinal pathogens in a murine model
Bouazzaoui, A., Huber, E., Dan, A., Al-Allaf, F. A., Pfirstinger, J., Sprotte, G., Köstler, J., Hiergeist, A., Gessner, A., Herr, W., et al. (2016) · Blood · doi:10.1182/blood-2016-06-722538 · Cited by 10
Zia, Y., Rajabi, A. A., Mi, S., Ju, T., Leonard, K., Nelson, R., Thiesen, A., Willing, B. P., Field, C. J., Curtis, J. M., et al. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy165 · Cited by 10
Crystal structure of monomeric Amuc_1100 from Akkermansia muciniphila
Mou, L., Peng, X., Chen, Y., Xiao, Q., Liao, H., Liu, M., Guo, L., Liu, Y., Zhang, X., & Deng, D. (2020) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x20004124 · Cited by 11
“A study has demonstrated that intestinal bacteria affect the physiology of the host by secreting various metabolites or bacterial products (Li et al., 2016).”
BackgroundOynotkinova, O. S., Nikonov, E. L., Demidova, T. Y., Baranov, A. P., Kryukov, E. V., Иванович, Д. Е., & Karavashkina, E. A. (2020) · Terapevticheskii arkhiv · doi:10.26442/00403660.2020.09.000784 · Cited by 14
Szabó, H., Piroska, M., Hernyes, A., Zoldi, L., Juhász, J., Ligeti, B., Makra, N., Szabó, D., Bikov, A., Kunos, L., et al. (2022) · Applied Sciences · doi:10.3390/app122211484 · Cited by 10
Xu, M., Lu, C. C., Hu, Y., Zhang, M., Shen, J., Liu, C., Lü, Q., & Liu, R. (2023) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250230 · Cited by 10
Evidence further linking the intestine to cardiovascular disease
Sulaiman, D., Reddy, S. T., & Fogelman, A. M. (2024) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000944 · Cited by 9
Zhao, J., Yuan, J., Zhang, Y., Deng, L., Pan, Y., Bai, X., Jia, L., Wang, Y., & Geng, W. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1421007 · Cited by 9
Cow’s Milk Bioactive Molecules in the Regulation of Glucose Homeostasis in Human and Animal Studies
Yuzbashian, E., Berg, E. V., Zani, S. C. D. C., & Chan, C. B. (2024) · Foods · doi:10.3390/foods13172837 · Cited by 9
“Akkermansia muciniphila increased in mice fed with milk PL, enhancing insulin sensitivity and protecting against inflammation caused by metabolic endotoxemia [177,178].”
BackgroundLiu, H., Feng, S., Tang, M., Tian, R., & Zhang, S. (2024) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2511395 · Cited by 9
“Many researchers have suggested that commensal microbiota functioned as an environmental factor contributing to metabolic disease [5], atherosclerotic lesions [3,6] and arterial thrombosis [7–9].”
Chen, Q., Huang, D., Liu, J., Jia, N., Shen, Z., Pei, C., Chen, C., Liu, Y., Wang, Y., Shi, S., et al. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1705487 · Cited by 11
The role of microbiota derived metabolites in modulating diabetic inflammation: a systematic review
Karthick, V., Thamarai, R., Amalraj, S., Kalimuthu, N., & Manimegalai, G. (2026) · Journal of Molecular Histology · doi:10.1007/s10735-026-10775-6 · Cited by 10
Human microbiome and cardiovascular diseases
Alam, J., Puppala, V., Uppulapu, S. K., Das, B., & Banerjee, S. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.07.012 · Cited by 11
Xing, M., Gao, H., Yao, L., Wang, L., Zhang, C., Zhu, L., & Cui, D. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1190954 · Cited by 9
“Akkermansia has also been reported to prevent the development of atherosclerosis (43), consistent with our findings.”
ResultZhang, B., Zeng, K., Li, R., Jiang, H., Gao, M., Zhang, L., Li, J., Guan, R., Liu, Y., Qiang, Y., et al. (2021) · Mathematical Biosciences & Engineering · doi:10.3934/mbe.2021427 · Cited by 9
Self-citationImpact of Trans ‐Fats on Heat‐Shock Protein Expression and the Gut Microbiota Profile of Mice
Carvalho, G. C. B. C., Moura, C. S., Roquetto, A. R., Arellano, D. B., Yamada, A. T., Santos, A., Saad, M. J. A., & Amaya-Farfán, J. (2018) · Journal of Food Science · doi:10.1111/1750-3841.13997 · Cited by 9
Evans, L., Price, T., Hubert, N., Moore, J., Shen, Y., Athukorala, M., Frese, S. A., Martinez, K., & Ferguson, B. S. (2023) · Biomolecules · doi:10.3390/biom13091274 · Cited by 8
“Consistent with this, Akkermansia supplementation reduced inflammation-induced damage and atherosclerosis in the hearts of Apolipoprotein E de-ficient mice fed a Western Diet [46].”
BackgroundLahoud, C., Habib, T., Kalta, D., Dimachkie, R., Sayegh, S. E. E., & Deeb, L. S. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14155260 · Cited by 9
“This was achieved by preventing endotoxins from being released into the body, which would have caused inflammation by inducing tight junction proteins, and thereby decreases gut permeability [22].”
Akkermansia muciniphila Alleviates Sarcopenia in Senescence-Accelerated Mouse-Prone 8 Mice
Park, S., Kim, H. S., Choi, P. G., Jeong, M. S., Huh, Y. H., Ahn, J., & Jung, C. H. (2025) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2507.07001 · Cited by 9
“These findings are consistent with those of previous studies demonstrating that A. muciniphila can mitigate the impairment of the intestinal barrier and suppress inflammation induced by metabolic endotoxemia [57, 58].”
Liu, L., Kaur, G. I. J., Kumar, A., Kanwal, A., & Singh, S. P. (2024) · Cardiovascular & Hematological Agents in Medicinal Chemistry · doi:10.2174/0118715257273506231208045308 · Cited by 8
Roessler, J., Zimmermann, F., Heidecker, B., Landmesser, U., & Haghikia, A. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14991 · Cited by 8
JAK1/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia
Young, A. P., & Denovan‐Wright, E. M. (2024) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-024-10115-z · Cited by 7
“In contrast, the abundance of A . muciniphila is negatively correlated with inflammatory bowel diseases, obesity and diabetes, as well as reduced disease severity in a mouse model of ALS (Everard et al. 2013; Chevalier et al. 2015; Li et al. 2016; Zhou 2017; Blacher et al. 2019).”
Extracellular vesicles in bone aging: therapeutic strategies and applications
Tang, L., Wang, P., Sheng, S., Yang, H., Jiang, Y., Jing, Y., Liu, H., & Su, J. (2025) · Extracellular Vesicles and Circulating Nucleic Acids · doi:10.20517/evcna.2025.58 · Cited by 9
Vorontsov, A., Kruglov, A., & Gubernatorova, E. O. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1733575 · Cited by 7
Gastrointestinal microbiome, what is behind faecal microbiota transplantation?
Pamela Thomson, M., Paulina Núñez, F., Quera, R., & Constanza Bay, M. (2021) · New Microbes and New Infections · doi:10.1016/j.nmni.2021.100898 · Cited by 7
Chen, C., Gao, K., Chen, Z., Zhang, Q., Ke, X., Mao, B., Fan, Q., Li, Y., & Chen, S. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1324691 · Cited by 8
Lee, H., Koh, G. Y., Lee, H., Alves, P. L. D. S., YOKOYAMA, W. H., & Wang, Y. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c09005 · Cited by 8
Akkermansia muciniphila, une bactérie pour lutter contre le syndrome métabolique
Plovier, H., & Cani, P. D. (2017) · médecine/sciences · doi:10.1051/medsci/20173304002 · Cited by 7
“muciniphila a également été montré pour d’autres pathologies comme l’athérosclérose [8].”
Lin, L., Wen, Z.-B., Lin, D.-J., Dong, J.-T., Jin, J., & Meng, F. (2018) · World Journal of Clinical Cases · doi:10.12998/wjcc.v6.i4.54 · Cited by 7
Noda, M., Maruyama, M., Danshiitsoodol, N., Higashikawa, F., & Sugiyama, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051896 · Cited by 10
Microbiome Medicine: Microbiota in Development and Management of Cardiovascular Diseases
Garg, Y., Kanwar, N., Chopra, S., Tambuwala, M. M., Dodiya, H. B., Bhatia, A., & Kanwal, A. (2022) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530322666220624161712 · Cited by 7
Li, X., Wang, Y., Zhang, J., Lu, G., You, Y., Wang, Y. H. D., Sun, H., Nan, B., & Wang, Y. (2022) · Journal of Food Biochemistry · doi:10.1111/jfbc.14372 · Cited by 7
Liu, J., Hefni, M. E., Witthöft, C. M., Bergström, M., Burleigh, S., NYMAN, M. E., & Hållenius, F. F. (2022) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2022.2106358 · Cited by 7
Ibrahim, Z., Khan, N. A., Qaisar, R., Saleh, M. A., Siddiqui, R., Al-Hroub, H. M., Giddey, A. D., Semreen, M. H., Soares, N. C., & Elmoselhi, A. B. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e23592 · Cited by 6
Hauser, G., Horvat, I. B., Rajilić-Stojanović, M. D., Zrnić, I. K., Kukla, M., Aljinović-Vučić, V., & Mikolašević, I. (2025) · Biomedicines · doi:10.3390/biomedicines13040779 · Cited by 8
Gut microbiota and its role in development of chronic disease and aging
Vesnina, A. D., Frolova, A. S., Chekushkina, D., Milentyeva, I., Luzyanin, S., & Aksenova, L. (2025) · Foods and raw materials · doi:10.21603/2308-4057-2026-1-668 · Cited by 8
Xu, Y., Fang, M., Chen, Z., Jin, Z., Zhang, T., Yu, L., Ma, F., Lu, Z., Wang, H., Zhang, L., et al. (2025) · Food Research International · doi:10.1016/j.foodres.2025.116537 · Cited by 6
Microbiome therapeutic PMC72 through reverse translational research in gout
Hossain, M. S., Seo, H., Lee, K., Ul-Haq, A., Kim, S., Jo, S., Rahim, M. A., Tajdozian, H., Ghorbanian, F., Yoon, Y., et al. (2025) · The Journal of Microbiology · doi:10.71150/jm.2501002 · Cited by 7
“For instance, Akkermansia muciniphila alleviates metabolic disorders, enhances the effectiveness of metformin in cancer treat-ment, and protects against atherosclerosis by reducing gut permeability and inflammation (Cuesta-Zuluaga et al., 2017; Li et al., 2016; Verdura et al., 2019).”
Emerging therapy targets to modulate microbiome-mediated effects evident in cardiovascular disease
Hoffelner, D. K., & Hendrikx, T. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1631841 · Cited by 6
Xu, Z., Wang, E., Wang, Y., Zhou, Y., Zeng, F., Luo, Y., Tan, Y., Jiang, Y., Zhao, C., & Hong, H. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.106979 · Cited by 7
Guan, Z., Xiao, W., Guan, Z., Xiao, J., Jin, X., Liu, S., Qin, Y., & Luo, L. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2555619 · Cited by 6
“27,28 In bone immunology studies, the balance of Th17/Treg and related inflammatory cytokines has been shown to be closely related to bone metabolic disorders.”
FakhriRavari, A., & Nguyen, M. H. (2025) · Gastrointestinal Disorders · doi:10.3390/gidisord7040072 · Cited by 7
Su, N., Han, S., Li, Z., Ling, X., Kong, L., & Song, D. (2025) · Applied and Environmental Microbiology · doi:10.1128/aem.01445-25 · Cited by 6
“Recent research has indicated that Akkermansia is instrumental in modulating gut barrier integrity and lipid metabolism in vivo (17, 25).”
Huang, J., Zhuang, W.-H., Lin, Y., Xu, J., Zhang, Y., Li, J., Huang, M., Xie, C., & Xu, R. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03590-5 · Cited by 7
“Additionally, gut microbiota-derived short-chain fatty acids (SCFAs) have been shown to modulate BBB permeability [33] and influence the integrity of BBB TJs [38, 39].”
Self-citationHu, X., Feng, J., Lü, J., Pang, R., Zhang, A., Liu, J., Gou, X., Bai, X., Wang, J., Chang, C., et al. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1395671 · Cited by 8
“Surprisingly, an increasing number of studies have shown that Akkermansia plays a key role in keeping the gastrointestinal tract intact and is considered the next generation of probiotics (Everard et al., 2013; Li et al., 2016; Munukka et al., 2018; Macchione et al., 2019; Wegierska et al., 2022).”
BackgroundGut microbiota: a new risk factor for atherosclerosis?
Drapkina, O. M., & Маратович, Ж. Л. (2022) · Russian Journal of Preventive Medicine · doi:10.17116/profmed20222511192 · Cited by 7
Gut Microbiota and Nutrition: Strategies for the Prevention and Treatment of Type 2 Diabetes
Sastre, M., Cimbalo, A., Mañes, J., & Manyes, L. (2024) · Journal of Medicinal Food · doi:10.1089/jmf.2022.0154 · Cited by 6
Qiu, Y., Hou, Y., Wei, X., Wang, M., Yin, Z., Xie, M., Duan, A., Ma, C., Si, K., & Wang, Z. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1267888 · Cited by 7
Effect of gut symbiotic bacteria Akkermansia muciniphila on aging-related obesity
Liu, Z., Chen, M., Zheng, W., Zhan, X., Sui, W., Huang, H., Jiang, Q., & Zhao, W. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151606 · Cited by 5
Guo, S., Yang, F., Zhang, J., Liao, Y., Xia, N., Tang, T., Wang, C., Wang, Q. K., Chen, C., Hu, D., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13040920 · Cited by 6
“The oral gavage of Akkermansia in mice was performed in accordance with the methods described in the previous literature, confirming that it significantly increased the abundance of this bacterium in the gut [19].”
The association between the health of the intestines and the human body with Akkermansia muciniphila
Tabatabaei, S. A. S., Ghadim, H. Y., Alaei, S., Abdolvand, F., Mazaheri, H., Shamsi, F., SarveAhrabi, Y., & Behrouzi, A. (2025) · The Microbe · doi:10.1016/j.microb.2025.100352 · Cited by 5
Yang, J., Shi, J., Xu, W., Mu, J., Chang, Y., Zhang, X., & Wang, X. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120458 · Cited by 5
Zhou, Y., Ren, X., Li, B., Tang, H., Guo, Y., Yang, L., Han, J. Z., & Zhou, B. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.5c12302 · Cited by 5
Xiong, M., Zhang, Z., Cui, J., Du, X., Chen, Y., & Zhang, T. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116916 · Cited by 5
Rieg, T., Xue, J., Stevens, M., Thomas, L., White, J. R., & Rieg, J. A. D. (2023) · Bioscience Reports · doi:10.1042/bsr20231217 · Cited by 5
Akkermansia muciniphila : a deworming partner independent of type 2 immunity
Wang, J., Zhao, X., Li, X., & Jin, X. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2338947 · Cited by 6
Wang, Z., Yang, S., Tong, L., Li, X., Mao, W., Yuan, H., Chen, Y., Zhang, S., Zhang, H., & Chen, R. (2024) · mSystems · doi:10.1128/msystems.00595-24 · Cited by 5
“The prominent bacterium Akkermansia muciniphila has been shown to serve as a protective shield against atherosclerosis in ApoE −/− mice by effectively reducing inflammation caused by metabolic endotoxemia (25).”
BackgroundLee, M., Ahn, K., & Kim, M. (2024) · PLoS ONE · doi:10.1371/journal.pone.0312670 · Cited by 6
Song, M., Cho, H., Lee, S., Lee, K. H., & Kim, W. (2022) · Life · doi:10.3390/life12020197 · Cited by 5
“5% cholesterol (Tables S1 and S2) [19] and exposed to the following interventions: control group (vehicle group), treated with normal saline; DSHT group, treated with 1000 mg/kg/day DSHT [20]; atorvastatin (AT) group, treated with 10 mg/kg/day AT [21]; DSHT and AT combination group (DSHT + AT group), treated with 1000…”
MethodAlterations in gut microbiota and physiological factors associated with abdominal aortic aneurysm
Zhang, K., Yang, S., Huang, Y., Qin, X., Qu, K., Chen, Y., Chen, L., Qiu, J., Hao, Y., & Wang, G. (2022) · Medicine in Novel Technology and Devices · doi:10.1016/j.medntd.2022.100122 · Cited by 5
Die Rolle des Darmmikrobioms bei chronischen Krankheiten: Eine narrative Übersichtsarbeit
Vijay, A., & Valdes, A. M. (2022) · Kompass Autoimmun · doi:10.1159/000524069 · Cited by 5
Gut Microbiota and Vascular Diseases: An Update
Wu, J., Li, Y., Yang, P., Fu, J., & Wang, Y. (2024) · Cardiovascular Innovations and Applications · doi:10.15212/cvia.2023.0090 · Cited by 6
“According to high throughput sequencing and animal studies, direct intake of probiotics effectively inhibits atherosclerotic progression [75, 76].”
BackgroundLimosilactobacillus fermentum KBL674 Alleviates Vaginal Candidiasis
Jang, S. J., Jo, E. J., Lee, C., Cho, B.-R., Shin, Y. J., Song, J. S., Kim, W.-K., Lee, N., Lee, H., Park, S., et al. (2024) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-024-10403-3 · Cited by 5
Ji, H., Dong, Z., Yang, Y., Cui, W., Han, J., Hu, Y., Chen, H., Qiao, C., Li, Q., Li, H., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156775 · Cited by 5
Zhang, C., Virk, A. K., KHAN, I. A., & Qin, H. (2020) · Springer eBooks · doi:10.1007/978-981-15-4759-1_2 · Cited by 5
Gut Microbiota: A New Regulator of Cardiovascular Function
Bulgakova, S. V., Захарова, Н. О., & Иванович, Р. П. (2021) · Bulletin of Science and Practice · doi:10.33619/2414-2948/62/20 · Cited by 5
Kumari, M., & Kokkiligadda, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822909-5.00004-6 · Cited by 5
Mukohda, M., Nakamura, S., Takeya, K., Matsuda, A., Yano, T., Seki, M., Mizuno, R., & Ozaki, H. (2021) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.121.000752 · Cited by 5
Designer Probiotics in Metabolic Disorders
Gupta, R. G., & Raghuwanshi, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-8444-9_12 · Cited by 5
Nitert, M. D. (2019) · Circulation Research · doi:10.1161/circresaha.118.314246 · Cited by 5
“The importance of Akkermansia in the pathogenesis of atherosclerosis has previously been indicated by a supplementation study with Akkermansia muciniphila, which prevented the development of atherosclerosis by western-style diet in the high risk Apoe mouse model.(10) This preventive effect was mediated by reduced cyto…”
BackgroundResultShi, S., Ji, X., Shi, J., Shi, S., Jia, Q., Yuan, G., Zhang, Q., Dong, Y. J., Lu, Y., Cui, H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.24.919316 · Cited by 5
Khalili, L., Park, G., Nagpal, R., & Salazar, G. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4771341 · Cited by 5
Linking gut, heart and metabolic health through cholesterol conversion by Akkermansia muciniphila
Kazemian, N., Karimianghadim, R., Golzan, S. A., Nitin, N., Irungu, J. D. W., Coombs, G. B., Low, J. L., Little, J. P., Zandberg, W. F., Halperin, F. A., et al. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.167391 · Cited by 5
Abolhassani, A., Moghadasian, M. H., Sedaghatnezhad, N., & Jafarnejad, S. (2025) · Heart and Mind · doi:10.4103/hm.hm-d-24-00161 · Cited by 5
Wu, J., Wang, B., Sha, X.-W., Wang, P., Du, S., Lu, X.-J., Miao, Z., Zhou, Y., & Zhao, X.-D. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117375 · Cited by 4
Intestinal Bacterium Akkermansia muciniphila Inhibits Progression of Abdominal Aortic Aneurysm
He, X., Liu, Y., Zhou, H., & Wu, K.-M. (2025) · Antioxidants and Redox Signaling · doi:10.1177/15230864251376034 · Cited by 5
“Increasing evidence indicates that Akk can alleviate vascular in fl ammation, improve endothelial function, and modulate gut – vascular interactions, thereby slowing the progression of vascular diseases such as atherosclerosis (Gofron et al., 2024; Hasani et al., 2021; Li et al., 2016).”
Chen, Y., Sui, J., Yu, Y., Zhang, H., Wesselius, A., Shen, Y., Qin, Q., Sun, G., Wang, S., Wang, X., et al. (2025) · BMC Medicine · doi:10.1186/s12916-025-04554-5 · Cited by 4
“At the occurrence stage of BC, PEA treatment led to an increased abundance of g_ Akkermansia , a genus within the p_ Verrucomicrobiota , which has been implicated in promoting anti-cancer effects through modulation of the immune microenvironment [74].”
Wild blueberries and cardiometabolic health: a current review of the evidence
Johnson, S. A., Klimis‐Zacas, D. J., Basu, A., Bolling, B. W., Feresin, R. G., Hooshmand, S., Joris, P. J., Li, Z., Lila, M. A., Stull, A. J., et al. (2026) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2025.2610406 · Cited by 5
“…dietary fiber and poly-phenols, has been shown to increase Akkermansia muciniphila in murine models and also suggesting that people with cardiometabolic disorders and lower levels of Akkermansia may benefit from increasing their intake of wild blueberries (Li et al. 2016; Luo et al. 2022).”
Zhu, Y., & Lǐ, Y. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1815352 · Cited by 4
“These effects are independent of lipid modulation (30).”
Zabolotneva, A. A., Popruga, K. E., Makarov, V. V., Yudin, S. M., Михайлович, Г. А., Roumiantsev, S. A., & Shestopalov, A. V. (2025) · Biomedicines · doi:10.3390/biomedicines13010183 · Cited by 4
“At the same time, the administration of A. muciniphila has been established to protect against atherogenesis in ApoE − / − mice [42,43].”
Lin, H., Shi, Z., Wang, B., Wang, S., He, J., & Zhang, W. (2025) · Food Research International · doi:10.1016/j.foodres.2025.116909 · Cited by 4
Chehade, S. B., Green, G. B. H., Graham, C. D., Chakraborti, A., Vashai, B., Moon, A., Williams, M. B., Vickers, B. N., Berryhill, T. F., Pol, W. V. D., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.929446 · Cited by 5
Uma, A., Sudarsanan, G. B., Karuppannan, A. K., & Palaniappan, S. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10165-4 · Cited by 5
“Contrary to expectations, despite being recognized as a mucin-degrading bacterium [39], A. muciniphila has been found to increase the thickness of the mucin layer [40].”
The association between flagellin producers in the gut microbiota and HDL-C level in humans
Yiu, J. H. C., Cai, J., Cheung, S. W. M., Chin, K. T.-C., Chan, C. F., C., E., Sharma, R., Dorweiler, B., & Woo, C. W. (2023) · Frontiers in Microbiomes · doi:10.3389/frmbi.2023.1287369 · Cited by 4
Self-citationNext -generation probiotics as potential therapeutic supplement for gastrointestinal infections
Gupta, N., Kachhawaha, K., Behera, D. K., & Verma, V. K. (2023) · Pharmacological Research - Reports · doi:10.1016/j.prerep.2024.100002 · Cited by 4
Yang, C., Chen, J., Zhou, H., Zeng, D., Wan, H., & Yang, J. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1394304 · Cited by 4
“Boosting the expression of the tight junction proteins ZO-1 and occludin, which in turn influences the function of the intestinal barrier, reduces the flow of lipopolysaccharides in the bloodstream, and reduces the inflammatory response in the body (Li et al., 2016).”
BackgroundQian, Z., Chen, S., Liao, X., Xie, J., Xu, Y., Zhong, H., Ou, L., Zuo, X., Xu, X., Peng, J., et al. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2474730 · Cited by 4
Deng, S., Chen, J., Liu, X., Dong, X., Zhang, X.-L., & Wang, G. (2022) · PubMed Central · doi:10.12182/20220160304 · Cited by 6
Platelets inhibit development of atherosclerosis in atherosclerotic mice
Liu, X., Bao, Y., Zhang, L., Tang, L., & Mao, P. (2022) · Cell Cycle · doi:10.1080/15384101.2022.2044703 · Cited by 4
“Similar to the changes in blood lipids reported in previous atherosclerosis studies [15,16], the present study showed that TC, TG, and LDL-C levels were significantly increased following 8 weeks of HFD, and the HDL-C level was significantly reduced.”
ResultApplication Potential of Probiotics in Acute Myocardial Infarction
Cai, J., & Jiang, H. (2022) · Cardiovascular Innovations and Applications · doi:10.15212/cvia.2022.0019 · Cited by 4
“…cure atherosclerotic lesion inflammation induced by a high sugar and high fat diet, decrease macrophage infiltration, decrease the expression of pro-inflammatory cytokines and chemokines, and significantly decrease endotoxemia, thus inhibiting the occurrence and development of atherosclerosis [82].”
Studying Fungal-Bacterial Relationships in the Human Gut Using an In Vitro Model (TIM-2)
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“31,32 43”
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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