Effect of betaine on alcohol-induced gut dysbiosis

Background: Alcohol-induced alterations in the gut microbiome and increased translocation of the gut luminal antigens via disrupted gut barrier have been associated with pathogenesis of alcoholic liver disease (ALD). Our... [ view full abstract ]

Background: Alcohol-induced alterations in the gut microbiome and increased translocation of the gut luminal antigens via disrupted gut barrier have been associated with pathogenesis of alcoholic liver disease (ALD). Our ongoing studies demonstrate that alcohol-induced gut barrier disruption and ALD pathogenesis are significantly mitigated by treatment with a dietary compound, betaine. In this study, we examined whether betaine-supplementation could also prevent/attenuate ethanol-induced alterations in gut microbiota (dysbiosis) and associated functional metabolic pathways.

Methods: Mice (n=5) were fed either control or ethanol diet supplemented with or without betaine for eight weeks. Genomic DNA was extracted from cecal samples for metagenomics sequencing using Illumina’s HiSeq platform. Taxonomic changes were compared by analyzing the resulting DNA sequences using MEGAN6 and STAMP metagenomics statistical software.

Results: Ethanol administration caused a significant reduction in the gram positive phyla, Firmicutes and Actinobacteria, and increased proportions of the gram negative phyla, Bacteroidetes and Proteobacteria. These ethanol-induced changes were prevented in mice fed a betaine-supplemented ethanol diet. Compared to controls, mice on the betaine-supplemented ethanol diet were low in the phylum Verrucomicrobia. At the genus level, ethanol administration increased Lactococcus/Streptococcus and reduced Bifidobacteria, Roseburia and Clostridia levels. These changes were significantly reversed by betaine co-supplementation. As expected, the changes in the gut microbiota correlated with alterations in metabolic functions. Specific functional pathways (Bacterial export protein family-3 and Agmatine-deiminase) affected by ethanol were restored by the betaine co-administration. 

Conclusions: Overall, ethanol-induced alterations in the gut microbiota were attenuated by betaine-co-administration. Thus, betaine may prove beneficial for mitigating ALD progression. 

Keywords: Alcoholic Liver Disease (ALD), Betaine, Gut Dysbiosis, Metagenomics, Microbiome