Normal Light-Dark and Short-Light Cycles Regulate Intestinal Inflammation, Circulating Short-chain Fatty Acids and Gut Microbiota in Period2 Gene Knockout Mice

Abstract

Regular environmental light–dark (LD) cycle-regulated period circadian clock 2 (Per2) gene expression is essential for circadian oscillation, nutrient metabolism, and intestinal microbiota balance. Herein, we combined environmental LD cycles with Per2 gene knockout to investigate how LD cycles mediate Per2 expression to regulate colonic and cecal inflammatory and barrier functions, microbiome, and short-chain fatty acids (SCFAs) in the circulation. Mice were divided into knockout (KO) and wild type (CON) under normal light–dark cycle (NLD) and short-light (SL) cycle for 2 weeks after 4 weeks of adaptation. The concentrations of SCFAs in the serum and large intestine, the colonic and cecal epithelial circadian rhythm, SCFAs transporter, inflammatory and barrier-related genes, and Illumina 16S rRNA sequencing were measured after euthanasia during 10:00–12:00. KO decreased the feeding frequency at 0:00–2:00 but increased at 12:00–14:00 both under NLD and SL. KO upregulated the expression of Per1 and Rev-erbα in the colon and cecum, while it downregulated Clock and Bmal1. In terms of inflammatory and barrier functions, KO increased the expression of Tnf-α, Tlr2, and Nf-κb p65 in the colon and cecum, while it decreased Claudin and Occludin-1. KO decreased the concentrations of total SCFAs and acetate in the colon and cecum, but it increased butyrate, while it had no impact on SCFAs in the serum. KO increased the SCFAs transporter because of the upregulation of Nhe1, Nhe3, and Mct4. Sequencing data revealed that KO improved bacteria α-diversity and increased Lachnospiraceae and Ruminococcaceae abundance, while it downregulated Erysipelatoclostridium, Prevotellaceae UCG_001, Olsenella, and Christensenellaceae R-7 under NLD in KO mice. Most of the differential bacterial genus were enriched in amino acid and carbohydrate metabolism pathways. Overall, Per2 knockout altered circadian oscillation in the large intestine, KO improved intestinal microbiota diversity, the increase in Clostridiales abundance led to the reduction in SCFAs in the circulation, concentrations of total SCFAs and acetate decreased, while butyrate increased and SCFAs transport was enhanced. These alterations may potentially lead to inflammation of the large intestine. Short-light treatment had minor impact on intestinal microbiome and metabolism.

Galactooligosaccharides ameliorate dietary advanced glycation end product-induced intestinal barrier damage in C57BL/6 mice by modulation of the intestinal microbiome

“…42 Meanwhile, our results for biomarkers with LDA > 4 of the bacterial flora showed that the dominant communities in the H-GOS group were Rikenella and Parabacteroides , compared with the AGE group. Rikenella was classified as a butyrate-producing bacterium, while Parabacteroides ASF519 and Parabacteroides johnsonii have been reported to produce propionate by succinate-conversion, 43–45 which was consistent with high-dose GOS supplementation leading to a significant increase in butyrate and propionate levels in AGE-induced mice. Accumulating evidence suggested that the cells lining the mucosa were affected by SCFAs in the intestinal lumen.…”

Sanghuangporus vaninii fruit body polysaccharide alleviates hyperglycemia and hyperlipidemia via modulating intestinal microflora in type 2 diabetic mice

“…It was suggested that Dubosiella may contribute to alleviation of insulin resistance and lipid metabolism. Interestingly, it was reported that the Erysipelatoclostridium is one of the dominant intestinal genera in obesity mice ( 61 ), which was considered to be harmful to human health ( 62 ). However, the relative abundance of Erysipelatoclostridium in this study was significantly positively associated with propionic acid, n -valeric acid, acetic acid, isovaleric acid, n -butyric acid, isobutyric acid and significantly negatively related to FFA level.…”

Association between rumen microbiota and marbling grade in Hu sheep

“…Previous studies have shown that ACADL , ALDH2 , FGFRL1 , SIX1 and PLCB1 are involved in fatty acid degradation, fatty acid metabolism and the PPAR signaling pathway ( Bedford et al, 2020 ; Fang et al, 2021 ; Shi et al, 2021 ). In addition, NHE1 and PCCA participate in butyric acid metabolism, phenylalanine metabolism and fatty acid metabolism ( Fu et al, 2022 ; Zhen et al, 2022 ). Our research found that acetate was used to form IMF lipid by the PPAR signaling pathway.…”