Integrated Gut Microbiota and Urine Metabolite Analyses of T2DM with NAFLD Rat Model

Appl Biochem Biotechnol. 2023 Nov;195(11):6478-6494. doi: 10.1007/s12010-023-04419-8. Epub 2023 Mar 4.

Abstract

Globally 80% type 2 diabetes mellitus (T2DM) patients suffer nonalcoholic fatty liver disease (NAFLD). The interplay of gut microbiota and endogenous metabolic networks has not yet been reported in the setting of T2DM with NAFLD. As such, this study utilized 16S rRNA gene sequencing to assess the changes in intestinal flora and nuclear magnetic resonance spectroscopy (1H NMR) to identify potential metabolites in a T2DM with NAFLD rat model. Spearman correlation analysis was performed to explore the relationship between gut microbiota and metabolites. Results revealed that among T2DM with NAFLD rats, diversity indexes of intestinal microbiota were distinctly decreased while levels of 18 bacterial genera within the intestinal tract were significantly altered. In addition, levels of eight metabolites mainly involved in the synthesis and degradation of ketone bodies, the TCA cycle, and butanoate metabolism were altered. Correlation analysis revealed that gut bacteria such as Blautia, Ruminococcus torques group, Allobaculum, and Lachnoclostridium strongly associate with 3-hydroxybutyrate, acetone, acetoacetate, 2-oxoglutarate, citrate, creatinine, hippurate, and allantoin. Our findings can provide a basis for future development of targeted treatments.

Keywords: 16S rRNA gene sequencing; Gut microbiota; Metabolites; Metabolomics; T2DM with NAFLD.

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / metabolism
  • Gastrointestinal Microbiome* / genetics
  • Humans
  • Magnetic Resonance Spectroscopy
  • Non-alcoholic Fatty Liver Disease*
  • RNA, Ribosomal, 16S / genetics
  • Rats

Substances

  • RNA, Ribosomal, 16S