Acetate differentially regulates IgA reactivity to commensal bacteria

Tadashi Takeuchi, Eiji Miyauchi, Takashi Kanaya, Tamotsu Kato, Yumiko Nakanishi, Takashi Watanabe, Toshimori Kitami, Takashi Taida, Takaharu Sasaki, Hiroki Negishi, Shu Shimamoto, Akinobu Matsuyama, Ikuo Kimura, Ifor R. Williams, Osamu Ohara and Hiroshi Ohno ()
Additional contact information
Tadashi Takeuchi: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Eiji Miyauchi: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Takashi Kanaya: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Tamotsu Kato: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Yumiko Nakanishi: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Takashi Watanabe: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences
Toshimori Kitami: YCI Laboratory for Cellular Bioenergetic Network, RIKEN Center for Integrative Medical Sciences
Takashi Taida: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Takaharu Sasaki: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Hiroki Negishi: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences
Shu Shimamoto: Tokyo Headquarters, Daicel Corporation
Akinobu Matsuyama: Tokyo Headquarters, Daicel Corporation
Ikuo Kimura: Kyoto University
Ifor R. Williams: Emory University School of Medicine
Osamu Ohara: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences
Hiroshi Ohno: Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences

Nature, 2021, vol. 595, issue 7868, 560-564

Abstract: Abstract The balance between bacterial colonization and its containment in the intestine is indispensable for the symbiotic relationship between humans and their bacteria. One component to maintain homeostasis at the mucosal surfaces is immunoglobulin A (IgA), the most abundant immunoglobulin in mammals1,2. Several studies have revealed important characteristics of poly-reactive IgA3,4, which is produced naturally without commensal bacteria. Considering the dynamic changes within the gut environment, however, it remains uncertain how the commensal-reactive IgA pool is shaped and how such IgA affects the microbial community. Here we show that acetate—one of the major gut microbial metabolites—not only increases the production of IgA in the colon, but also alters the capacity of the IgA pool to bind to specific microorganisms including Enterobacterales. Induction of commensal-reactive IgA and changes in the IgA repertoire by acetate were observed in mice monocolonized with Escherichia coli, which belongs to Enterobacterales, but not with the major commensal Bacteroides thetaiotaomicron, which suggests that acetate directs selective IgA binding to certain microorganisms. Mechanistically, acetate orchestrated the interactions between epithelial and immune cells, induced microbially stimulated CD4 T cells to support T-cell-dependent IgA production and, as a consequence, altered the localization of these bacteria within the colon. Collectively, we identified a role for gut microbial metabolites in the regulation of differential IgA production to maintain mucosal homeostasis.

Date: 2021
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DOI: 10.1038/s41586-021-03727-5

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