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Updated: May 22, 2026

Applying Advanced In Vitro Culturing Technology to Study the Human Gut Microbiota
Published on: February 15, 2019
Epigenetic phase variation in the gut microbiome enhances bacterial adaptation
Mi Ni1, Katerina Junker2, Yujie Liu1
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
None:
The human microbiome continuously adapts to variations in diet and host physiology. Epigenetic phase variation (ePV) mediated by bacterial DNA methylation can generate phenotypic heterogeneity within clonal populations. ePVs have been characterized in human pathogens, but their roles in commensals remain unclear. Here, we cataloged ePVs in infant and adult gut microbiomes, revealing genome-wide and site-specific ePV in response to antibiotics and fecal microbiota transplantation. Long-read metagenomics revealed genome-wide ePV mediated by structural variations of DNA methyltransferases. Analysis of public short-read metagenomic datasets further revealed a high prevalence of genome-wide ePVs in the human microbiome. Site-specific ePVs were identified and associated with antibiotics or probiotic engraftment. Focusing on an Akkermansia muciniphila isolate, we find a specific ePV regulating mucC, a gene of unknown function but whose heterologous expression enhances bacterial tolerance to antibiotics via a bet-hedging strategy. Thus, epigenetic modifications are used by gut bacteria to adapt to fluctuating environments.
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