Gut Microbiota Profile Changes in Patients with Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease: A Metagenomic Study

Abstract

Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. β-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation.

Keywords: IBD; NAFLD; gut microbiota; leaky gut; liver steatosis.

Figure 1

α-diversity assessed by Shannon Index (A) and β-diversity assessed by PCoA (B) compared between the four study groups. PCoA: Principal Coordinate Analysis.

Figure 2

Results in the comparison between IBD-only group and CTRLs according to α-diversity assessed by Shannon Index (A), Bacteroidetes/Firmicutes ratio (B), and OTUs analysis assessed by LDA score (C); between NAFLD-only group and CTRLs according to Bacteroidetes/Firmicutes ratio (D), and OTUs analysis assessed by LDA score (E). LDA scores can be interpreted as the degree of difference in the relative abundance of OTUs. IBD: Inflammatory Bowel Disease, CTRLs: healthy controls, OTUs: Operational Taxonomic Units, LDA: Linear Discriminant Analysis, NAFLD: Non-Alcoholic Fatty Liver Disease.

Figure 3

Differential abundance at genus level according to LDA score in the IBD-NAFLD group compared with CTRLs. LDA scores can be interpreted as the degree of difference in the relative abundance of OTUs. LDA: Linear Discriminant Analysis, IBD-NAFLD: Inflammatory Bowel Disease Non-Alcoholic Fatty Liver Disease, CTRLs: healthy controls.

Figure 4

Results in the comparison between IBD-only group and NAFLD-only group according to α-diversity assessed by Shannon Index (A), β-diversity assessed by PCoA (B), Bacteroidetes/Firmicutes ratio (C), differential abundance at phylum (D) and species (E) level. IBD: Inflammatory Bowel Disease, NAFLD: Non-Alcoholic Fatty Liver Disease, PCoA: Principal Coordinate Analysis.

Figure 5

Results in the comparison between NAFLD-only group and IBD-NAFLD group according to Bacteroidetes/Firmicutes ratio (A) and differential abundance at genus level according to LDA score (B); between IBD-only group and IBD-NAFLD group according to α-diversity assessed by Shannon Index (C), Bacteroidetes/Firmicutes ratio (D) and differential abundance at genus level according to LDA score (E). LDA scores can be interpreted as the degree of difference in the relative abundance of OTUs. IBD: Inflammatory Bowel Disease, NAFLD: Non-Alcoholic Fatty Liver Disease, PCoA: Principal Coordinate Analysis, LDA: Linear Discriminant Analysis.