Constitution of mucosa‐associated microbiota in the lower digestive tract does not change in early stage of non‐alcoholic fatty liver disease with fecal dysbiosis

Abstract

Background and Aim Regarding the gut–liver axis, fecal dysbiosis is implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The significance of mucosa‐associated microbiota (MAM, which is present in the mucin layer covering the intestinal mucosa) has not been well explored. We aimed to clarify the characteristics of MAM in patients with NAFLD. Methods MAM were obtained from seven patients with early‐stage NAFLD and seven controls by colonoscopy in five locations (terminal ileum, cecum, ascending and sigmoid colon, and rectum) using mucosal brushes. The microbial 16S rDNA profiles of the MAM and fecal microbiota of patients in the NAFLD and control groups were analyzed. Results α‐diversities of fecal microbiota were decreased in patients with NAFLD (observed species, Shannon index, and Chao1: 174.57 vs 134.86, 5.51 vs 4.65, and 206.34 vs 167.91; P = 0.048, 0.067, and 0.087, respectively), and microbial composition analyses by principal coordinate analysis differed between the fecal microbiota of patients with NAFLD and those of controls (permutational analysis of variance [PERMANOVA] of weighted and unweighted: Pseud‐ F : 1.4179/ P ‐value: 0.05 and Pseud‐ F : 2.1497/ P ‐value: 0.049, respectively). However, α‐diversities or microbial composition of MAM in most parts of the intestine did not differ significantly between the NAFLD and control groups. Unclassified Rikenellaceae , Oscillospira, Odoribacter, unclassified clostridiales , and Holdemania were decreased in the feces of patients with NAFLD (determined by linear discriminant analysis effect size), but five (except Holdemania ) of the six genera were not decreased in the MAM of these patients. Conclusion In early‐stage NAFLD, MAM was uniform and relatively stable throughout the intestine, even when fecal dysbiosis appeared.

Changes in the intestinal microbiota of individuals with non-alcoholic fatty liver disease based on sequencing: An updated systematic review and meta-analysis

“…The sequencing protocol was performed in all studies, of which 71.43% (20/28) [ 14 , 16 , 18 – 21 , 23 – 27 , 29 – 32 , 34 – 38 ] involved 16S rRNA gene sequencing. Approximately 60.71% (17/28) [ 12 – 16 , 18 , 19 , 22 , 25 , 26 , 30 , 31 , 33 , 35 , 36 , 38 , 39 ] of the studies were conducted in Asia, 17.86% (5/28) [ 21 , 23 , 27 , 29 , 32 ] in Europe, 17.86% (5/28) [ 17 , 20 , 28 , 34 , 37 ] in North America, and only 3.57% (1/28) [ 24 ] in South America. Because only one study in South America was insufficient for subgroup analysis, studies other than those in Asia were uniformly categorized as studies from other continents.…”

“…Alpha diversity provides a prediction of species richness and evenness and is measurable by the Shannon, Simpson, and Chao indices. A total of 21 papers reported the Shannon index [ 13 , 14 , 18 , 21 , 22 , 26 , 29 – 31 , 34 , 39 ]. Among them, Asaji [ 22 ] et al collected samples that contained mucus from different intestinal segments (including the terminal ileum, cecum, transverse colon, sigmoid colon, and rectum), in addition to feces.…”

Composition of gut microbiota and non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

“…A total of 38 studies 11–21,33,35,36,38–41,44–46,48,49,51–53,56,58–62,64–66,68–71,74,75,78,79,82,84 provided data for α‐diversity (Table 1), which was then assessed using eight indices, namely richness/evenness (Shannon [ n = 37, 3186 cases, and 3990 controls]）, Chao1 [ n = 16, 1002 cases, and 1824 controls], Simpson [ n = 12, 488 cases, and 419 controls]), estimates of richness (observed species [ n = 10, 836 cases, and 813 controls], richness [ n = 7, 791 cases, and 1354 controls], faith phylogenetic diversity [PD, n = 6, 761 cases, and 1936 controls], evenness [Pielou, n = 6, 552 cases, and 185 controls]), and abundance coverage estimator (ACE; n = 4, 64 cases and 73 controls).…”

“…A total of 38 studies [11][12][13][14][15][16][17][18][19][20][21]33,35,36,[38][39][40][41][44][45][46]48,49,[51][52][53]56,[58][59][60][61][62][64][65][66][68][69][70][71]74,75,78,79,82,84 provided data for α-diversity (Table 1), which was then assessed using eight indices, namely richness/evenness (Shannon T A B L E 2 Total analysis, stratified analysis, and sensitivity analysis among alpha diversity.…”

“…A total of 47 studies [11][12][13][14][15][16][17][18][19][20][21][33][34][35][36][38][39][40][41][43][44][45]48,49,51,52,55,[57][58][59][60][61][62][63][64][65][66]68,69,73,75,[77][78][79][81][82][83] reported data for β-diversity (Table 1), 25 studies reported results by using the weighted or unweighted Unifrac method to calculate distance, 17 studies used the Bray-Curtis method, and few studies used various methods (Figure 3 and Appendix S7). Significant differences in β-diversity were reported by over 75% (37/47) of the included studies, and the remain...…”