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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
An obesity-associated gut microbiome with increased capacity for energy harvest
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
Human gut microbes associated with obesity
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Inflammation and Atherosclerosis
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Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
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Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
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Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J.-J., Blugeon, S., Bridonneau, C., Furet, J.-P., Corthier, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804812105 · Cited by 4,413
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Intestinal mucosal barrier function in health and disease
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Yanamadala, Y., Muthumula, C. M. R., Gokulan, K., Karn, K., Sutherland, V. L., CUNNY, H. C., Santos, J. H., & Khare, S. (2025) · Experimental Biology and Medicine · doi:10.3389/ebm.2025.10564 · Cited by 3
Ma, L., Li, N., Zhao, Z., Zhao, Y., Yang, G., Zhao, L., & Li, S. (2025) · Nutrients · doi:10.3390/nu17193027 · Cited by 3
“Moreover, the enrichment of Akkermansia has been shown to be beneficial for improving atherosclerosis [30].”
Ahmed, L. A., & Al‐Massri, K. F. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178210 · Cited by 3
da Silva, J. T. S., & Nagata, C. L. P. (2021) · Nutrire · doi:10.1186/s41110-021-00150-8 · Cited by 3
“After 45 consecutive days of supplementation, the abundance of Akkermansia muciniphila, bacteria with anti-inflammatory properties [32, 33], increased substantially (p < 0.”
BackgroundConclusion and future perspective
Chauhan, N. S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99336-4.00001-x · Cited by 3
Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children
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“Western-diet-induced dysbiosis has been associated with increased circulating endotoxin and inflammatory markers, and increased atherosclerosis in a murine model [36].”
BackgroundMicrobiome-Based Formulations and Products and Their Therapeutic Implications
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Gut microbiota dynamics of adult and sub‐adult sika deer during reintroduction
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Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria
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“Additionally, specific bacterial metabolites, including imidazole propionate, branched-chain amino acids, and SCFAs, can disrupt insulin signaling and glucose metabolism, contributing to diabetes and obesity [119].”
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“MR ‒ Egger regression in the reverse MR analysis did not yield significant results for horizontal pleiotropy (Supplementary Table 12).”
Gut microflora and metabolic syndrome: new insight into the pathogenesis of hypertension
Mukohda, M., Mizuno, R., & Ozaki, H. (2022) · Folia Pharmacologica Japonica · doi:10.1254/fpj.22035 · Cited by 4
Han, G., Лю, Б., Wang, C., Wang, D., Li, Q., Cai, Q.-L., & Kong, D. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c01487 · Cited by 3
Akkermansia muciniphila: Obezite ve Diyabetten Korunmada Yeni Bir Alternatif Olabilir mi?
Ekici, L., & Kaya, H. P. (2019) · European Journal of Science and Technology · doi:10.31590/ejosat.563713 · Cited by 3
Copper fabric improves the metabolic profile of obese mice: Potential role of the gut microbiota
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Clostridium butyricum Ameliorates Atherosclerosis by Regulating Host Linoleic Acid Metabolism
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“Mono-colonization of Akkermansia muciniphila ( A. muciniphila ) in Apoe − / − mice reduced gut permeability and ameliorated endotoxaemia-induced vascular inflammation, thereby alleviating AS (Li et al. 2016).”
Li, Y., Sun, Y., Wang, X., Liu, M., Luo, Y., Wang, X., & Zhang, H. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c05681 · Cited by 3
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“Mounting evidence indicates that gut microbiota dysbiosis contributes to the pathogenesis of CAD through multiple mechanisms, including low-grade endotoxemia, altered short-chain fatty acid production, and bile acid dysregulation [11, 12].”
The Microbiome Epoch: Cracking the Cardiovascular-Neurodegenerative Disorder Code
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Shi, C., Gao, Y., Zhang, L., CHEN, C. X. R., 苏立松, Ren, K., Liu, Z., & Liu, J. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1861538 · Cited by 2
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“Присутствие в микрофлоре Akkermansia muciniphila ассоциировано с противовоспалительным, иммуномодулирующим влиянием микробиоты на организм пациента, а также с более совершенным гомеостазом глюкозы и функцией эндотелия [25, 39].”
It’s not a gut feeling – fruit and vegetables do have prebiotic-like effects
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Predictors of arterial hypertension in children (A Review)
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A gut bacterium tackles atherosclerosis
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Targeting gut microbiota to regulate the adaptive immune response in atherosclerosis
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Measurement Method of Akkermansia Muciniphila by Graphene-Based Transistor for Diseases Diagnosis
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“muciniphila is closely related to the healthy host and its concentration is inversely correlated with many diseases, such as, diet-induced obesity [4], diabetes mellitus [5], gut barrier dysfunction [6], atherosclerosis lesions [7], and cancer immunotherapy [8].”
BackgroundHealth effects and potential mode of action of papaya (Carica papayaL.) bioactive chemicals
Desjardins, Y. (2019) · Acta Horticulturae · doi:10.17660/actahortic.2019.1250.28 · Cited by 2
Beneficial Modulation of the Gut Microbiome: Probiotics and Prebiotics
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Mysterious Akkermansia muciniphila. What do we know about it? A review
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Faecal Transplant Therapy: A Promising Treatment Modality for Cardiovascular Diseases
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Potential Role of SGLT2 Inhibitors in the Treatment and Prevention of Diabetic Cardiomyopathy
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Intestinales Mikrobiom und kardiovaskuläre Erkrankungen
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“Dieser anti-atherosklerotische Effekt war nur mit lebenden, nicht aber mit hitzeinaktivierten Bakterien zu erzielen [16].”
BackgroundJiang, Z., Xiao, C., Zhang, X., Zhao, M., Liu, T., Xu, Y., Zhang, H., Zheng, J., & Feng, F. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.11.294454 · Cited by 2
“syndrome and systemic low-grade inflammation (30, 31), but our results suggested that GML 260 treatments could significantly decrease Akkermansia muciniphila and Lupinus luteus, and increase 261 Ruminococcus gnavus, which were adverse to reduce the serum LPS concentration and 262 pro-inflammatory cytokines (32), and m…”
ResultLiu, Y., Wu, H., Liu, B., Chen, S., Huang, L., Liu, Z., Wang, J., Xie, L., & Wu, X. (2022) · Research Square · doi:10.21203/rs.3.rs-2346866/v1 · Cited by 2
Wang, Y., He, J., Chen, S., Lv, X., Chen, J., Ru, K., Liang, X., Mao, M., & Song, Y. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1569241 · Cited by 2
Chen, R., Li, R., Jiang, J., Zhou, L., Zhao, S., Zhang, Y., Xia, Q., & Yang, Z. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1585640 · Cited by 1
Lin, K., Lee, S., Ya-Jy, L., Wu, P., Chang, T., Chang, W.-L., & Yen, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125856 · Cited by 1
“Akkermansia , a mucin-degrading bacterium, is known to enhance intestinal barrier integrity and suppress inflammation [28,48].”
Akkermansia muciniphila: A Promising Next Generation Probiotic
Hasnain, M. A., & Moon, G. (2025) · Current Topic in Lactic Acid Bacteria and Probiotics · doi:10.35732/ctlabp.2025.11.1.1 · Cited by 1
Functional Proteins of Akkermansia Muciniphila: Impacts on Host Health and Metabolism
Safari, F., Golafshan, F., Malekpour, E., Mirzaei, S. A., Rouzbahani, H., Hajarzadeh, M. O., Harandi, S. N., Nasirharandi, S., & Noursina, A. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10871-1 · Cited by 1
“…showing that replenishment with A. muciniphila reverses atherosclerotic lesion formation by specifically inducing the expression of tight junction pro - teins (ZO-1 and occludin), leading to decreased systemic inflammation and reduced macrophage infiltration within the plaques themselves [10].”
Patial, S., Raj, K., & Shukla, G. (2026) · BMC Microbiology · doi:10.1186/s12866-026-04840-z · Cited by 1
“Similarly, Li et al. [14] demonstrated that administration of Akkermansia muciniphila to ApoE¯/¯ mice receiving a Western-type diet attenuated aortic lesion development and vascular inflammation, mainly by limiting macrophage infiltration and up-regulating claudin and occludins tight junctions [14].”
Wu, Q., Hu, K., Wang, Q., Luo, T., Hu, L., Liu, J., Zou, D., Hu, J., & Guo, Z. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01668-5 · Cited by 1
Wang, W., Feng, C., Lou, Y., Liu, C., Chang, G., Xu, K., Ren, W., Luo, M., Hu, Y., & Zhu, L. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107325 · Cited by 1
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“A. muciniphila has been proposed as a potential “next-genera-tion probiotic” because it may contribute to maintenance of the mucosal barrier, immune regulation, and inflammatory responses (Cani et al., 2022; Li et al., 2016; Zeng et al., 2023).”
Dumlao, J. M., McCallum, P., Hodak, C. R., Guinto, E., Enns, W., Davey, L. E., & Choy, J. C. (2026) · BMC Microbiology · doi:10.1186/s12866-026-05202-5 · Cited by 1
“Oral gavage of mice with A. muciniphila protects against inflammatory bowel disease, obesity, insulin resistance, atherosclerosis, and some cancers [19, 22-25].”
Song, H.-J., Eom, J.-E., Lim, E. Y., Kim, S., Lee, S.-Y., Shin, H. S., Jeong, D. Y., Kang, C.-H., & Kim, G.-D. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119577 · Cited by 1
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“…the family Tannerellaceae and genus Akkermansia , both reported to exert protective effects in liver disease and atherosclerosis development, 26,27 showed the largest decrease in relative abundance in ethanol-consuming mice, while Muribaculaceae displayed a markedly increased relative…”
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Akkermansia muciniphila and Its Bioactive Derivatives: Emerging Regulators of Healthy Aging
Zhang, T., Niu, J., Hu, X., Hu, Z., Gao, Y., Liu, J., Chen, N., & Hu, Y. (2026) · Aging Cell · doi:10.1111/acel.70702 · Cited by 1
“…abundance for patient stratification (Mount et al. 2026; Zhang, Liu, et al. 2025), serum inflammatory and barrier integrity markers (such as LPS and TNF-α) to identify responders (Li et al. 2016), baseline cancer screening for safety and strain-level functional genotyping to match aging phenotypes.”
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Akkermansia mucinifila and the part that it plays in metabolic disturbance
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“There are several studies where Akkermansia municiphila is specifically associated with a healthy gut, as it has been proved its ability to reverse atherosclerotic lesions, to improve the restoration of the intestinal barrier and reduce endotoxin-induced metabolic inflammation [48,55].”
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Role of Hepatic PEMT and Dietary Choline in the Development of Atherosclerosis
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MICROBIOTA INTESTINALE E RISCHIO CARDIOVASCOLARE
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“muciniphila покращує бар’єрну функцію кишечника та чинить протиатеросклеротичну дію [18, 19].”
The Factors Influencing Gut Microbiota in Autoimmune Diseases
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Faecalibacterium prausnitzii Reduces Plasma Lipopolysaccharide and Inhibits AtherosclerosisPreprint
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Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infectionPreprint
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Probiotics as a Sustainable Approach in Health Enrichment
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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
About these checks
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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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