Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis

Abstract

There is increasing evidence for the role of gut microbial composition in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is the most serious form of NAFLD where inflammation causes liver damage that can progress to cirrhosis. We have characterized the gut microbiome composition in UK patients with biopsy-proven NASH (n = 65) and compared it to that in healthy controls (n = 76). We report a 7% lower Shannon alpha diversity in NASH patients without cirrhosis (n = 40) compared to controls (p = 2.7x 10 −4) and a 14% drop in NASH patients with cirrhosis (n = 25, p = 5.0x 10 −4). Beta diversity (Unweighted UniFrac distance) was also significantly reduced in both NASH (p = 5.6x 10 −25) and NASH-cirrhosis (p = 8.1x 10 −7) groups. The genus most strongly associated with NASH in this study was Collinsella (0.29% abundance in controls, 3.45% in NASH without cirrhosis (False Discovery Rate (FDR) p = .008), and 4.38% in NASH with cirrhosis (FDR p = .02)). This genus, which has been linked previously to obesity and atherosclerosis, was also positively correlated with fasting levels of triglycerides (p = .01) and total cholesterol (p = 1.2x 10 −4) and negatively correlated with high-density lipoprotein cholesterol (p = 2.8x 10 −6) suggesting that some of the pathways present in this microbial genus may influence lipid metabolism in the host. In patients, we also found decreased abundance of some of the Ruminococcaceae which are known to produce high levels of short-chain fatty acids which can lower inflammation. This may thus contribute to pathology associated with NASH.

The Impact of Probiotics Supplementation on Gut Microbiota after <i>Helicobacter pylori </i>Eradication: A Multicenter, Open-Label, Randomised Trial

“…There were important taxonomic changes at the genus level after treatment. BQT treatment at week Sutterella, and Collinsella, mainly contributing to the digestive disorder, inflammation, abnormal lipids metabolism and various metabolic syndrome [28][29][30][31]. However, we did not observed much valuable difference at week 6 and week 8 between the two groups, probably because the probiotics supplementation was abolished in this period.…”

“…These discrepant observations may be explained partially by different eradication regimens, drug doses and treatment duration lengths. In addition, other factors, such as dietary habit, previous antibiotic treatment history, and individual differences in the absorption rate for antibiotics, can affect the influence of eradication therapy on gut microbiota [25]. In our present study, we evaluated the food intake and baseline characteristics in each subjects and observed there was no obvious difference in the diet components and baseline characteristics.…”

“…The V3-V4 hypervariable regions of the 16S rRNA were amplified using the following primers: forward Primer: 5'-ACTCCTACGGGAGGCAGCAG-3' and reverse primer 5'-GGACTACHVGGGTWTCTA AT-3'. The amplifications were performed employing a step cycling protocol consisting of 95 °C for 30 min, 25…”

De novo species identification using 16S rRNA gene nanopore sequencing

“…Our study confirms the vaginal delivery association for Parabacteroides distasonis and Bacteroides fragilis ( Shao et al, 2019 ; Stewart et al, 2018 ), while Bacteroides xylanisolvens and Collinsella aerofaciens have not yet been linked to vaginal delivery in the literature. B. xylanisolvens is a xylan- degrading bacterium in adults ( Chassard et al, 2008 ) with the potential to induce an IgM response towards glucan antigens ( Ulsemer et al, 2016 ), while C. aerofaciens is a proinflammatory gut bacterium that has previously been associated with nonalcoholic fatty liver in adults ( Astbury et al, 2020 ). Since both bacteria are potential immunomodulators in the adult gut, they may play a role in the proper maturation of the immune system of infants ( Rodriguez et al, 2015 ).…”

Complete Genome Sequence of Collinsella aerofaciens JCM 10188 T

“…Collinsella spp. are considered pathobionts, being associated with diseases such as irritable bowel syndrome (1), psoriatic arthritis (2), nonalcoholic steatohepatitis (3), and symptomatic atherosclerosis (4). Elevated abundance of Collinsella was also correlated with rheumatoid arthritis (5), with Collinsella aerofaciens being experimentally demonstrated to increase gut permeability and augmented arthritis severity in mice.…”