Endocrine Abstracts

Dysbiosis of the gut microbiome contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Reduced diversity and composition of the microbiome are associated with increased intestinal barrier permeability, increased bacterial translocation and NAFLD progression. The ALIOS diet in rodents replicates many of the metabolic and histological features of NAFLD in humans and here we report the effect of the ALIOS diet on the gut microbiome. Male and female C57BL/6 mice were fed normal chow (NC) or an ALIOS diet (45% fat [30% trans-fat], 55% fructose: 45% glucose in H2O) for 52 weeks and caecal samples sent for 16S amplicon sequencing. The composition of the microbiome was altered in the ALIOS mice. Principal coordinate analysis showed a difference in diversity between ALIOS vs NC fed mice (P<0.01) although this was reduced (P<0.1) when weighted for relative abundance. The ALIOS diet decreased bacterial diversity within samples. Shannon entropy was reduced in ALIOS-fed mice (n=17: 9 female, 8 male) compared to NC (n=13: 8 female, 5 male) (ALIOS: 5.53±0.19 vs NC: 6.19±0.33, P<0.05, data are mean±SEM). Pielou evenness was reduced in ALIOS-fed mice compared to NC (ALIOS: 0.62±0.15 vs NC: 0.69±0.19, P<0.01, data are mean±SEM). The ALIOS diet altered the relative abundance of microbes at different taxonomic levels. Phyla analysis revealed no difference in Firmicutes/Bacteroidetes ratio, however, compared to NC, ALIOS-fed mice had increased Acidobacteria (P<0.01), Chloroflexi (P<0.01), Gemmatimonadetes (P<0.01), Nitrospirae (P<0.01), Verrucomicrobia (P<0.01) and Latescibacteria (P<0.05). ANCOM analysis revealed ALIOS-fed mice had enrichment of the genus Lactococcus (W=4310), and species Lactobacillus salivarius (W=4237). Whereas the families Muribaculaceae (W=4247) and Lachnospiraceae (W=4229), and genera Prevotella (W=4180) and Ruminococcus (W=3927) were reduced. In conclusion, ALIOS-fed mice had reduced microbiome diversity and altered composition that may contribute to the NAFLD phenotype observed in these mice.