Association of colitis with gut-microbiota dysbiosis in clathrin adapter AP-1B knockout mice

Aditi Jangid; Shinji Fukuda; Masahide Seki; Terumi Horiuchi; Yutaka Suzuki; Todd D Taylor; Hiroshi Ohno; Tulika Prakash

doi:10.1371/journal.pone.0228358

Association of colitis with gut-microbiota dysbiosis in clathrin adapter AP-1B knockout mice

PLoS One. 2020 Mar 24;15(3):e0228358. doi: 10.1371/journal.pone.0228358. eCollection 2020.

Authors

Aditi Jangid¹, Shinji Fukuda^{2

3

4}, Masahide Seki⁵, Terumi Horiuchi⁵, Yutaka Suzuki⁵, Todd D Taylor⁶, Hiroshi Ohno³, Tulika Prakash⁶

Affiliations

¹ BioX Centre and School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India.
² Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
³ Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa, Japan.
⁴ Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
⁵ Department of Computational Biology and Medical Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
⁶ Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.

Abstract

Inflammatory bowel disease results from alterations in the immune system and intestinal microbiota. The role of intestinal epithelial cells (IECs) in maintaining gut homeostasis is well known and its perturbation often causes gastrointestinal disorders including IBD. The epithelial specific adaptor protein (AP)-1B is involved in the establishment of the polarity of IECs. Deficiency of the AP-1B μ subunit (Ap1m2-/-) leads to the development of chronic colitis in mice. However, how this deficiency affects the gut microbes and its potential functions remains elusive. To gain insights into the gut microbiome of Ap1m2-/- mice having the colitis phenotype, we undertook shotgun metagenomic sequencing analysis of knockout mice. We found important links to the microbial features involved in altering various physiological pathways, including carbohydrate metabolism, nutrient transportation, oxidative stress, and bacterial pathogenesis (cell motility). In addition, an increased abundance of sulfur-reducing and lactate-producing bacteria has been observed which may aggravate the colitis condition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Protein Complex 1 / deficiency*
Adaptor Protein Complex 1 / genetics*
Animals
Colitis / complications
Colitis / genetics*
Colitis / microbiology*
Dysbiosis / complications
Dysbiosis / microbiology*
Gastrointestinal Microbiome*
Metagenomics
Mice

Substances

Adaptor Protein Complex 1

Grants and funding

This study was supported in part by Japan Society For The Promotion of Science (JSPS) KAKENHI (grant no. 18H04805 to S.F.), Japan Science and Technology Agency (JST) PRESTO (grant no. JPMJPR1537 to S.F.), JST ERATO (grant no. JPMJER1902 to S.F.), Advanced Research & Development Programs for Medical Innovation (AMED-CREST; grant no. JP19gm1010009 to S.F.), the Takeda Science Foundation (to S.F.), the Food Science Institute Foundation (to S.F.), the Program for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative (to S.F.). This study was also supported in part by JSPS KAKENHI (grant no. 16H06279 to Y.S.). The Council of Scientific and Industrial Research, India provided support in the form of a fellowship to AJ. TP received support in the form of salary from IIT Mandi. In addition, the HPC facility at IIT Mandi has been used for bioinformatics analysis. RIKEN provided material support and support in the form of salaries for TT and HO. The specific roles of these authors are articulated in the ‘author contributions’ section.