Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders

Aron‐Wisnewsky, Judith; Vigliotti, Chloé; Witjes, Julia J.; Le, Phuong Thi; Holleboom, Adriaan G.; Verheij, Joanne; Nieuwdorp, Max; Clément, Karine

doi:10.1038/s41575-020-0269-9

Cited by 691 publications

(544 citation statements)

References 187 publications

(446 reference statements)

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“…At the family level, reduced Bacteroidaceae , an unclassifiable family of the order Bacteroidales ( Bacteroidales;other ) but increased Actinomycetaceae and Lachnospiraceae were observed in F3/4 patients. Similar to our findings, a consistent association between increased Proteobacteria and NAFLD has been reported previously, 37‐39 whereas associations between other phylum and NAFLD and fibrosis have been discordant 39 . For example, both increased and decreased Bacteroides have been reported to be associated with advanced fibrosis/cirrhosis using metagenomic methods 38,40 .…”

Section: Discussionsupporting

confidence: 91%

“…For example, both increased and decreased Bacteroides have been reported to be associated with advanced fibrosis/cirrhosis using metagenomic methods 38,40 . Reduced Bacteroidaceae has previously been found to be associated with cirrhosis, whereas in contrast to our findings, reduced Lachnospiraceae has been documented to be associated with cirrhosis, although this may be related to falling faecal BA levels in the setting of decompensation 35,39 . The associations between Actinomycetaceae have not been previously reported to our knowledge and need to be confirmed in larger cohorts.…”

Section: Discussioncontrasting

confidence: 86%

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Bile acids associate with specific gut microbiota, low‐level alcohol consumption and liver fibrosis in patients with non‐alcoholic fatty liver disease

Adams

Wang

Liddle

et al. 2020

Liver International

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Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. Results: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 86%

Bile acids associate with specific gut microbiota, low‐level alcohol consumption and liver fibrosis in patients with non‐alcoholic fatty liver disease

Adams

Wang

Liddle

et al. 2020

Liver International

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“…In brief, steatosis and NASH patients have increased abundance of Proteobacteria (13.5%) at the phylum level, increased Enterobacteriaceae (12.02%) and decreased Rikenellaceae (0.41% in NASH versus 1.97% in healthy patients) and Ruminococcaceae (7.01% in NASH versus 18.82% in healthy patients) at the family levels, and increased Escherichia (2.36% versus 0.3% in healthy patients), Peptoniphilus (4.1% versus 0.36% in healthy patients) and decreased Anaerosporobacter (1.08% versus 2.02% in healthy patients), Coprococcus (1.03% versus 3.69% in healthy patients), Eubacterium (0.29% versus 1.18% in healthy patients), Faecalibacterium (4.27% versus 8.15% in healthy patients) and more discordant changes in Prevotella at the genera level (6,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The authors did acknowledge that despite these differences there is widespread divergence in the literature across all levels of taxonomy, with some studies even reporting trends opposite to the ones discussed above (10).…”

Section: Microbiome and Human Nafldmentioning

confidence: 99%

“…an unhealthy change in the normal bacterial ecology, also known as dysbiosis, and all stages of NAFLD, including fatty liver, NASH, advanced fibrosis and also cirrhosis and hepatocellular carcinoma (10). Aron-Wisnewsky et al divided human studies into steatosis to NASH, and NAFLD fibrosis to NASH cirrhosis signatures.…”

Section: Microbiome and Human Nafldmentioning

confidence: 99%

Can You Trust Your Gut? Implicating a Disrupted Intestinal Microbiome in the Progression of NAFLD/NASH

Jadhav

Cohen

2020

Front. Endocrinol.

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disorders, ranging from fatty liver to a more insulin resistant, inflammatory and fibrotic state collectively termed nonalcoholic steatohepatitis (NASH). In the United States, 30%-40% of the adult population has fatty liver and 3%-12% has NASH, making it a major public health concern. Consumption of diets high in fat, obesity and Type II diabetes (T2D) are wellestablished risk factors; however, there is a growing body of literature suggesting a role for the gut microbiome in the development and progression of NAFLD. The gut microbiota is separated from the body by a monolayer of intestinal epithelial cells (IECs) that line the small intestine and colon. The IEC layer is exposed to luminal contents, participates in selective uptake of nutrients and acts as a barrier to passive paracellular permeability of luminal contents through the expression of tight junctions (TJs) between adjacent IECs. A dysbiotic gut microbiome also leads to decreased gut barrier function by disrupting TJs and the gut vascular barrier (GVB), thus exposing the liver to microbial endotoxins. These endotoxins activate hepatic Toll-like receptors (TLRs), further promoting the progression of fatty liver to a more inflammatory and fibrotic NASH phenotype. This review will summarize major findings pertaining to aforementioned gut-liver interactions and its role in the pathophysiology of NAFLD.

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“…The changes of gut microbiota may disrupt the gut tight junctions, leading to increased gut permeability and LPS translocation. Increased LPS translocation induces "metabolic endotoxemia, " which triggers inflammatory reactions, insulin resistance, and promotes the development of NAFLD (Leung et al, 2016;Aron-Wisnewsky et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Constant Light Exposure Alters Gut Microbiota and Promotes the Progression of Steatohepatitis in High Fat Diet Rats

et al. 2020

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Background: Non-alcoholic fatty liver disease (NAFLD) poses a significant health concern worldwide. With the progression of urbanization, light pollution may be a previously unrecognized risk factor for NAFLD/NASH development. However, the role of light pollution on NAFLD is insufficiently understood, and the underlying mechanism remains unclear. Interestingly, recent studies indicate the gut microbiota affects NAFLD/NASH development. Therefore, the present study explored effects of constant light exposure on NAFLD and its related microbiotic mechanisms. Materials and Methods: Twenty-eight SD male rats were divided into four groups (n = 7 each): rats fed a normal chow diet, and exposed to standard light-dark cycle (ND-LD); rats fed a normal chow diet, and exposed to constant light (ND-LL); rats fed a high fat diet, and exposed to standard light-dark cycle (HFD-LD); and rats on a high fat diet, and exposed to constant light (HFD-LL). Body weight, hepatic pathophysiology, gut microbiota, and short/medium chain fatty acids in colon contents, serum lipopolysaccharide (LPS), and liver LPS-binding protein (LBP) mRNA expression were documented post intervention and compared among groups. Result: In normal chow fed groups, rats exposed to constant light displayed glucose abnormalities and dyslipidemia. In HFD-fed rats, constant light exposure exacerbated glucose abnormalities, insulin resistance, inflammation, and liver steatohepatitis. Constant light exposure altered composition of gut microbiota in both normal chow and HFD fed rats. Compared with HFD-LD group, HFD-LL rats displayed less Butyricicoccus, Clostridium, and Turicibacter, butyrate levels in colon contents, decreased colon expression of occludin-1 and zonula occluden−1 (ZO-1), and increased serum LPS and liver LBP mRNA expression. Conclusion: Constant light exposure impacts gut microbiota and its metabolic products, impairs gut barrier function and gut-liver axis, promotes NAFLD/NASH progression in HFD rats.

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Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders

Cited by 691 publications

References 187 publications

Bile acids associate with specific gut microbiota, low‐level alcohol consumption and liver fibrosis in patients with non‐alcoholic fatty liver disease

Bile acids associate with specific gut microbiota, low‐level alcohol consumption and liver fibrosis in patients with non‐alcoholic fatty liver disease

Can You Trust Your Gut? Implicating a Disrupted Intestinal Microbiome in the Progression of NAFLD/NASH

Constant Light Exposure Alters Gut Microbiota and Promotes the Progression of Steatohepatitis in High Fat Diet Rats

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