What Is the Association Between Gut Microbiota and Nonalcoholic Fatty Liver Disease?

Certain gut microbiota may contribute to the progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) may develop in accordance with the abundance of gut microbiota, according to a study in Digestive and Liver Disease.

Investigators conducted a 2-sample Mendelian randomization (MR) analysis to assess the causal relationship between NAFLD and gut microbiota (GM) at the phylum, class, order, family, and genus taxonomic levels.

Gut microbiome data were obtained from the MiBioGen consortium. The study involved 18,340 participants from 24 population-based cohorts in 11 countries.

Summary data were collected regarding associations between NAFLD and genetic factors from a systematic analysis of a genome-wide association study of 8434 cases and 770,180 control individuals of European descent. The systematic analysis included 4 cohorts.

Increasing the number of Lactobacillaceae, Intestinibacter, and Christensenaceae may alleviate NAFLD.

Researchers classified 211 bacterial taxa into 5 taxonomic levels, and 196 bacterial groups were included in the genera classification. A total of 2160 single-nucleotide polymorphisms (SNPs) were used as instrumental variables, and 114 SNPs from 10 microbial taxa features with a genome-wide significance level were included in the MR analysis.

Lactobacillaceae (odds ratio [OR], 0.83; 95% CI, 0.72-0.95; P =.007), Christensenellaceae (OR, 0.74; 95% CI, 0.59-0.92; P =.007), and Intestinibacter (OR, 0.85; 95% CI, 0.73-0.99; P =.035) were negatively correlated with NAFLD, according to the inverse variance weighted analysis.

Coriobacteriia (OR, 1.22; 95% CI, 1.01-1.42; P = .038), Actinomycetales (OR, 1.25; 95% CI, 1.02-1.53; P =.031), Coriobacteriales (OR, 1.22; 95% CI, 1.01-1.42; P =.038), Actinomycetaceae (OR, 1.25; 95% CI, 1.02-1.53; P =.032), Coriobacteriaceae (OR, 1.22; 95% CI, 1.01-1.48; P =.038), Oxalobacteraceae (OR, 1.10; 95% CI, 1.01-1.21; P =.036), and Ruminococcaceae_UCG005 (OR, 1.18; 95% CI, 1.01-1.38; P =.033) had a positive association with NAFLD.

The leave-one-out analysis yielded strong evidence for the robustness of the findings in the MR analysis, as the exclusion of any individual instrumental variable did not significantly affect the overall results.

Limitations include the use of genome-wide data from European populations and smaller samples from other ethnic groups. Also, further understanding of the pathways involved in the interplay between related metabolites and NAFLD is needed, as are deeper mechanistic studies and validations focusing on metabolic comorbidities, ethnicity, and severity of liver disease.

“Our results suggest a causal relationship between some specific strains and NAFLD,” study authors noted. “Increasing the number of Lactobacillaceae, Intestinibacter, and Christensenaceae may alleviate NAFLD. On the contrary, suppressing the abundance of Actinomycetales, Actinomycetaceae, Actinobacteria, Coriobacteriia, Coriobacteriales, Ruminococcaceae_UCG005, and Oxalobacteriaceae in the gut may be potential treatment targets for NAFLD.”

This article originally appeared on Gastroenterology Advisor


Li Y, Liang X, Lyu Y, et al. Association between the gut microbiota and nonalcoholic fatty liver disease: a 2-sample Mendelian randomization study. Dig Liver Dis. Published online August 3, 2023. doi:10.1016/j.dld.2023.07.014