High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice (July 5, 2016)

Biological Sciences 2016/07/05

Shinsaku Okai, Fumihito Usui, Shuhei Yokota, Yusaku Hori-i, Makoto Hasegawa, Toshinobu Nakamura, Manabu Kurosawa, Seiji Okada, Kazuya Yamamoto, Eri Nishiyama, Hiroshi Mori, Takuji Yamada, Ken Kurokawa, Satoshi Matsumoto, Masanobu Nanno, Tomoaki Naito, Yohei Watanabe, Tamotsu Kato, Eiji Miyauchi, Hiroshi Ohno, Reiko Shinkura

Dysbiosis of gut microbiota disrupts intestinal homeostasis and causes inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis (UC), and extra-intestinal disorders including allergies, asthma, metabolic syndrome, cardiovascular diseases, and obesity. Hence restoration of gut microbiota symbiosis is key to the prevention and treatment of a wide range of diseases. One of the promising agents shown to shape the gut microbiota community is intestinal IgA, which is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defense against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood.
The Shinkura group at NAIST isolated monoclonal IgA antibodies from small intestines of healthy mice. As a candidate for the efficient gut microbiota modulator, they selected a monoclonal IgA antibody W27 that had strong binding ability against a variety of bacteria and suppressed the cell growth of E. coli via an epitope-specific binding, but neither bound to nor suppressed Lactobacillus casei in vitro. W27 can distinguish non-beneficial bacteria from beneficial ones through recognition of four amino acid sequences of a bacterial metabolic enzyme, serine hydroxymethyltransferase. In gut lumen, orally given W27 modulated commensal microbiota composition towards symbiotic balance, resulting in beneficial effects on several dysbiosis-associated intestinal disease models in mice. Thus W27 IgA oral treatment is a potential remedy not only for inflammatory bowel disease but also extra-intestinal disorders, acting through restoration of the host-microbial symbiosis.

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