Interplay of Lymphocytes with the Intestinal Microbiota in Children with Nonalcoholic Fatty Liver Disease

Abstract

Abnormally high lymphocyte counts are seen in persons with nonalcoholic fatty liver disease (NAFLD). Gut microbiota dysbiosis is a risk factor for NAFLD. We assessed the gut microbiota of 63 healthy children and 63 children with NAFLD using 16S rRNA gene and metagenomic sequencing to explore the relationships. Compared with healthy children (HC group), the Bacteroidetes, Verrucomicrobia, and Akkermansia were less abundant, while the Actinobacteria were more abundant in children with NAFLD (FLD group). To understand the effect of lymphocytes on the gut microbiota of children with NAFLD, we compared the microbiota of 41 children with NAFLD and high numbers of lymphocytes (FLD_HL group) and 22 children with NAFLD and low numbers of lymphocytes (FLD_LL group). The abundances of Bacteroidetes, Verrucobacterium, and Akkermansia increased and Actinobacteria decreased in the FLD_LL group compared to the FLD_HL group. Akkermansia was negatively correlated with lymphocyte count. NAFLD may disturb the gut microbiota in children through reducing the abundance of Akkermansia and increasing the abundance of proinflammatory bacteria, such as Escherichia-Shigella. Conclusions: High lymphocyte counts are associated with disturbances of gut microbiota and emergence of opportunistic pathogens in children with NAFLD.

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

“…The majority of studies were case–control studies (56/63), two cohorts, four cross‐sectional studies, and one experimental study. Twelve studies were conducted among children 20,39,44,51,55,56,64,67,71,74,80,83 . Regarding the individual studies, the total number of included participants varied from 14 to 1544 (median 75).…”

“…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).…”

“…Twelve studies were conducted among children. 20,39,44,51,55,56,64,67,71,74,80,83 Regarding the individual studies, the total number of included participants varied from 14 to 1544 (median 75). Over half of the studies (40 [63.5%]) were conducted in Eastern countries, and 23 (36.5%) were conducted in Western countries.…”

“…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...…”