FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis.

Abstract

The physiological homeostasis of gut mucosal barrier is maintained by both genetic and environmental factors and its impairment leads to pathogenesis such as inflammatory bowel disease. A cytokine like molecule, FAM3D (mouse Fam3D), is highly expressed in mouse gastrointestinal tract. Here, we demonstrate that deficiency in Fam3D is associated with impaired integrity of colonic mucosa, increased epithelial hyper-proliferation, reduced anti-microbial peptide production and increased sensitivity to chemically induced colitis associated with high incidence of cancer. Pretreatment of Fam3D-/- mice with antibiotics significantly reduces the severity of chemically induced colitis and wild type (WT) mice co-housed with Fam3D-/- mice phenocopy Fam3D-deficiency showing increased sensitivity to colitis and skewed composition of fecal microbiota. An initial equilibrium of microbiota in cohoused WT and Fam3D-/- mice is followed by an increasing divergence of the bacterial composition after separation. These results demonstrate the essential role of Fam3D in colon homeostasis, protection against inflammation associated cancer and normal microbiota composition.

• Authors: Weiwei Liang, Xinjian Peng, Qingqing Li, Pingzhang Wang, Ping Lv, Quansheng Song, Shaoping She, Shiyang Huang, Keqiang Chen, Wanghua Gong, Wuxing Yuan, Vishal Thovarai, Teizo Yoshimura, Colm O'huigin, Giorgio Trinchieri, Jiaqiang Huang, Shuye Lin, Xiaohong Yao, Xiuwu Bian, Wei Kong, Jianzhong Xi, Ji Ming Wang, Ying Wang
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 5912 (11 20 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 33219235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• FAM3D protein, mouse
• Pore Forming Cytotoxic Proteins

Topics

• Animals
• Carcinogenesis
• Colitis
• Colon (metabolism, microbiology, pathology)
• Colorectal Neoplasms
• Cytokines (metabolism)
• Disease Models, Animal
• Gastrointestinal Microbiome
• Inflammation
• Inflammatory Bowel Diseases
• Intestinal Mucosa (growth & development, pathology)
• Mice
• Pore Forming Cytotoxic Proteins (metabolism)