Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice

Jennifer T. Wolstenholme, Justin M. Saunders, Maren Smith, Jason D. Kang, Phillip B. Hylemon, Javier González-Maeso, Andrew Fagan, Derrick Zhao, Masoumeh Sikaroodi, Jeremy Herzog, Amirhossein Shamsaddini, Marcela Peña-Rodríguez, Lianyong Su, Yun Ling Tai, Jing Zheng, Po Cheng Cheng, R. Balfour Sartor, Patrick M. Gillevet, Huiping Zhou, Jasmohan S. Bajaj

Research output: Contribution to journalArticlepeer-review

Abstract

Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans.

Original languageEnglish
Article number6198
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

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