Altered microbial community structure in PI3Kγ knockout mice with colitis impeding relief of inflammation: Establishment of new indices for intestinal microbial disorder.

Abstract

Lipopolysaccharide stimulates the intestinal microbiome to activate phosphoinositide 3 kinase (PI3K) signaling via several pathways; however, the direct effect that PI3K has on the intestinal bacterial community remains unclear. Herein, we investigate changes in the colonic microbiome of colitis PI3Kγ-knockout (PI3Kγ-/-) mice. Additionally, the effect of anal administration of colonic irrigation fluid from control mice to those with colitis was examined. Microbial 16S rRNA genes from the colonic mucosa of PI3Kγ-/- and WT mice were sequenced using Illumina MiSeq platform, and colonic IgA, IL-2, IL-10, and IL-17A production was quantified by western blot analysis. Myeloperoxidase (MPO) activity was detected by absorbance via colorimetric analysis. From the results, two new indices were derived by dividing the bacterial community into invading taxa, common taxa, and vanishing taxa. These indices were used to estimate the degree of microbiome disorder in chronic experimental colitis models. PI3Kγ-/- mice showed slower remission of inflammation as assessed by the disease activity index，pathological score, IL-2, IL-17, IL-10, IgA expression and MPO activity. The unique and common taxa of wild-type and PI3Kγ-/- mice increased as colitis symptoms regressed. Continuous loss of commensal bacteria happened with the continuous invasion of exogenous bacteria in the intestinal mucosa of PI3Kγ--/- mice after colitis begin to aggravate. However, transplantation of normal intestinal microbiota to PI3Kγ-/- mice promoted remission of inflammation; while the microbial dysbiosis observed during PI3Kγ dysfunction aggravated the intestinal microbiome disorder and impeded colitis recovery. Thus, the PI3Kγ signaling pathway may regulate microbial community composition in the colon.

• Authors: Yi Li, Qian-Qian Chen, Jian Yuan, Zheng Chen, Hai-Tao Du, Jun Wan
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 79 Pg. 105901 (Feb 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 31896510 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Cytokines
• RNA, Ribosomal, 16S
• Trinitrobenzenesulfonic Acid
• Class Ib Phosphatidylinositol 3-Kinase
• Pik3cg protein, mouse

Topics

• Animals
• Class Ib Phosphatidylinositol 3-Kinase (genetics, metabolism)
• Colitis (chemically induced, immunology, microbiology)
• Colon (immunology, microbiology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Humans
• Inflammatory Bowel Diseases (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Microbiota
• RNA, Ribosomal, 16S (genetics)
• Signal Transduction
• Trinitrobenzenesulfonic Acid