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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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50 Own result · 43 Not checked yet · 13 Own interpretation · 2 Own method · 1 Partly supported · accuracy not yet measured
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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
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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
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
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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
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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
plain- Asserted: passes — The authors put it forward as true.
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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
“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
plain- Asserted: passes — The authors put it forward as true.
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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
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 36
- Probably not a substantial claim. 32
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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
- Partly supportedcites [41] sourceExperimental — accuracy not yet measured
The Abstract reports that people with endotoxin levels above 50 pg/ml had about threefold higher odds of incident carotid atherosclerosis, supporting the clinical risk-factor claim. The paper’s discussion of experimental evidence does not report weekly lipopolysaccharide injections or their effect on atherosclerosis formation in animals. (LLM, conf=0.88)
- Not checked yetcites [42]
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“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
plain- Asserted: passes — The authors put it forward as true.
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- 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
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“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
plaindirectn = 8- Asserted: passes — The authors put it forward as true.
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- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plainn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ 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
“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”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > CLINICAL PERSPECTIVE
“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.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > Abstract
“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”
§ Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe -/-Mice > References
“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.”
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The gut microbiota as a novel regulator of cardiovascular function and disease
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“This bacterium also contributes to the decrease in adipose tissue inflammation by reducing macrophage infiltration, restoring regulatory T cells (Treg cells), reducing pro-inflammatory cytokines (such as IL 6 and IL-1β), and increasing anti-inflammatory factors (such as α-tocopherol and β-sitosterol) [109, 111, 115].”
BackgroundInteractions between gut microbiota and polyphenols: A mechanistic and metabolomic review
Cheng, H., Zhang, D., Wu, J., Liu, J., Zhou, Y., Tan, Y., Feng, W., & Peng, C. Y. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154979 · Cited by 194
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“muciniphila and obesity and other diseases [14, 18, 34].”
Jian, H., Liu, Y., Wang, X., Dong, X., & Zou, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043900 · Cited by 186
“As explained above, Akk can ameliorate gut barrier impairment in the cases of obesity [22,39,40,47], metabolic diseases [71,76,85], inflammation [85,122,123], and aging [125,129–132]; therefore, it is necessary to know how”
BackgroundInfluentialUtilization of the microbiome in personalized medicine
Ratiner, K., Ciocan, D. M., Abdeen, S. K., & Elinav, E. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00998-9 · Cited by 189
“Supplementation of Akkermansia muciniphila featured promising results in animal models of obesity and insulin resistance, response to anticancer immunotherapy 93 , amyotrophic lateral sclerosis 94 and atherosclerosis 95 .”
Jennis, M., Cavanaugh, C., Leo, G. C., Mabus, J. R., Lenhard, J. M., & Hornby, P. J. (2017) · Neurogastroenterology & Motility · doi:10.1111/nmo.13178 · Cited by 173
A. Muciniphila Suppresses Colorectal Tumorigenesis by Inducing TLR2/NLRP3-Mediated M1-Like TAMs
Fan, L., Xu, C., Ge, Q., Lin, Y., Wong, C. C., Qi, Y., Ye, B., Lian, Q., Zhuo, W., Si, J., et al. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-1019 · Cited by 178
Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases
Liu, M., Yang, J.-Y., Yan, Z.-H., Hu, S., Li, J.-Q., Xu, Z., & Jian, Y. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.08.029 · Cited by 176
Self-citationβ-glucans: a potential source for maintaining gut microbiota and the immune system
Singh, R. P., & Bhardwaj, A. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1143682 · Cited by 181
“A previous study showed that oat-β-glucan promotes the expansion of the Verrucomicrobia population (such as Akkermansia muciniphila), which has a prebiotic impact on alterations in circulatory lipids and decreases the number of plaques in the aortic walls as compared with simvastatin (is an oral antilipemic agent) (21…”
BackgroundLuo, Z., Xia, K., Liu, Y.-W., Liu, J., Rao, S., Hu, X., Chen, C., Xu, R., Wang, Z., & Xie, H. (2021) · International Journal of Nanomedicine · doi:10.2147/ijn.s304515 · Cited by 167
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“The probiotic effects of A. muciniphila have been studied extensively in animals and clinical studies, and the potential mechanisms were reported from cell biology studies (Derrien et al., 2011; Everard et al., 2013; Lukovac et al., 2014; Li et al., 2016).”
BackgroundMicrobiome therapeutics: exploring the present scenario and challenges
Yadav, M., & Chauhan, N. S. (2021) · Gastroenterology report · doi:10.1093/gastro/goab046 · Cited by 164
“Akkermansia muciniphila relieves metabolic disorders and cooperates with the use of metformin in cancer therapeutics [20] as well as protects against atherosclerosis by reducing gut permeability and preventing inflammation [21].”
The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease
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Plant phenolics as functional food ingredients
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Cheng, H., Liu, J., Zhang, D., Wang, J., Tan, Y., Feng, W., & Peng, C. Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.817600 · Cited by 147
“As a type of bacteria that settles on the mucus layer and uses mucin as a source of nutrition, the relative abundance of Akkermansia has been reported to be negatively correlated with intestinal inflammation and the Akkermansia species can enhance the function of the intestinal barrier by promoting tight junctions in…”
BackgroundInfection and atherosclerosis: TLR-dependent pathways
Li, B., Xia, Y., & Hu, B. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03453-7 · Cited by 149
Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis
Thye, A. Y.-K., Bah, Y.-R., Law, J. W.-F., Tan, L. T.-H., He, Y.-W., Wong, S.-H., Thurairajasingam, S., Chan, K.-G., Lee, L.-H., & Letchumanan, V. (2022) · Biomedicines · doi:10.3390/biomedicines10051037 · Cited by 156
Butyrate-producing bacteria and the gut-heart axis in atherosclerosis
Chen, W., Zhang, S., Wu, J., Ye, T., Wang, S., Wang, P., & Xing, D. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.04.037 · Cited by 150
Yan, J., Pan, Y., Shao, W., Wang, C., Wang, R., He, Y., Zhang, M., Wang, Y., Li, T., Wang, Z., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01390-0 · Cited by 150
“05% cysteine (Sigma– Aldrich) at 37°C for 2–3 days [70].”
BackgroundInfluentialEffects of subchronic oral toxic metal exposure on the intestinal microbiota of mice
Zhai, Q., Li, T., Yu, L., Xiao, Y., Feng, S., Wu, J., Zhao, J., Zhang, H., & Chen, W. (2017) · 中国科学通报：英文版 · doi:10.1016/j.scib.2017.01.031 · Cited by 145
Potential Benefits of Probiotics and Prebiotics for Coronary Heart Disease and Stroke
Wu, H., & Chiou, J. A. (2021) · Nutrients · doi:10.3390/nu13082878 · Cited by 153
“Intake of low-dose LPS in animal models resulted in vascular inflammation and atherosclerosis [52,53].”
BackgroundNext-generation probiotics: a promising approach towards designing personalized medicine
Singh, T. P., & Nataraj, B. H. (2021) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1902940 · Cited by 150
“Moreover, Li et al. (2016) reported that administration of A. muciniphila could reverse the atherosclerotic lesions, improve metabolic endotoxemia-induced inflammation, and ultimately, restore the gut barrier in Apoe–/– mice.”
BackgroundAstaxanthin Prevents Alcoholic Fatty Liver Disease by Modulating Mouse Gut Microbiota
Liu, H., Liu, M., Fu, X., Zhang, Z., Zhu, L., Zheng, X., & Liu, J. (2018) · Nutrients · doi:10.3390/nu10091298 · Cited by 137
“Akkermansia is a dominant genus in Verrucomicrobia and can degrade intestinal mucin [42], increasing mucus thickness and enhancing gut barrier function, which correlates inversely with the incidence of inflammation [43] and metabolic syndrome [18].”
BackgroundAkkermansia muciniphila : is it the Holy Grail for ameliorating metabolic diseases?
Yan, J., Sheng, L., & Li, H. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1984104 · Cited by 143
“muciniphila reduced intestinal permeability by increasing the expression of occludin and ZO-1 in Apoe mice.(20) Similarly, Zhao et al.”
BackgroundCheng, H., Liu, J., Tan, Y., Feng, W., & Peng, C. Y. (2021) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2021.10.003 · Cited by 140
Postbiotics: metabolites and mechanisms involved in microbiota-host interactions
Peluzio, M. D. C. G., Martinez, J. A., & Milagro, F. I. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2020.12.004 · Cited by 139
Coronary artery disease is associated with an altered gut microbiome composition
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Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases
Tu, P., Chi, L., Bodnar, W. M., Zhang, Z., Gao, B., Bian, X., Stewart, J. R., Fry, R. C., & Lü, K. (2020) · Toxics · doi:10.3390/toxics8010019 · Cited by 136
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Zhao, L. B., Chen, J., Bai, B., Song, G., Zhang, J., Han, Y., Huang, S., Wang, Z., & Lu, G. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1333986 · Cited by 154
Jiang, Z., Zhao, M., Zhang, H., Yang, L., Liu, M., & Feng, F. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700547 · Cited by 126
“Specific and significant increase of Akkermansia muciniphila (widely considered as mucos-protection bacterium) [34-36] in the gut was important for reducing the host”
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Atorvastatin Treatment Modulates the Gut Microbiota of the Hypercholesterolemic Patients
Khan, T. J., Ahmed, Y. M., Zamzami, M. A., Siddiqui, A. M., Khan, I., Baothman, O. A. S., Mehanna, M. G., Kuerban, A., Mohammed, K., & Yasir, M. (2018) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2017.0130 · Cited by 117
“…proin-flammatory bacteria and taxa associated with atherosclerosis formation and CVD progression (Gregory et al., 2015; Karls-son et al., 2012; Koren et al., 2011) and increase the abundance of health beneficial bacteria, particularly the anti-inflammatory taxa (Li et al., 2016; Rossi et al., 2016).”
InfluentialMilk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits
Anto, L., Warykas, S. W., Torres‐Gonzalez, M., & Blesso, C. N. (2020) · Nutrients · doi:10.3390/nu12041001 · Cited by 119
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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