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Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.

ABSTRACT: BACKGROUND:The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "beneficial" microbes to rescue busulfan induced mucositis. RESULTS:In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in "beneficial" microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the "beneficial" microbe Lactobacillales helped with the recovery of blood metabolites, while the "harmful" microbe Mycoplasmatales did not. CONCLUSION:The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract.

SUBMITTER: Zhang P

PROVIDER: S-EPMC7382812 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.

Zhang Pengfei P Liu Jing J Xiong Bohui B Zhang Cong C Kang Beining B Gao Yishan Y Li Zengkuan Z Ge Wei W Cheng Shunfeng S Hao Yanan Y Shen Wei W Yu Shuai S Chen Liang L Tang Xiangfang X Zhao Yong Y Zhang Hongfu H

Microbiome 20200725 1

<h4>Background</h4>The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "benef ...[more]

PMID: 32711581

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Project description:Alginate oligosaccharide (AOS), prepared from depolymerised alginate, a natural polysaccharide occurring in the cell walls of brown algae, provides beneficial effects for intestinal health. However, the underlying mechanisms by which AOS supplementation maintains the intestinal integrity of weaned pigs remain obscure. Here, we aimed to determine how AOS modulates the intestinal integrity of weaned pigs. Twenty-four weaned pigs were assigned to two treatments: a control group (basal diet) and an AOS group (the basal diet supplemented with 100 mg kg-1 AOS). On day 15, eight pigs per treatment were randomly selected and sacrificed for serum and intestinal samples. We observed that AOS supplementation enhanced the intestinal integrity, as evidenced by the increased (P < 0.05) intestinal occludin protein abundance. Compared to the control group, AOS ingestion both elevated (P < 0.05) the jejunal and ileal catalase activity and decreased (P < 0.05) the duodenal and jejunal tumour necrosis factor-α concentration and mast cell tryptase expression. Furthermore, AOS down-regulated (P < 0.05) the duodenal toll-like receptor 4 (TLR4) and its down-stream signals, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1) and tumour necrosis factor receptor-associated factor 6 (TRAF6) mRNA levels, as well as jejunal nucleotide-binding oligomerisation domain protein 1 (NOD1) and its adaptor molecule, receptor-interacting serine/threonine-protein kinase 2 (RIPK2), mRNA levels. Additionally, phospho-nuclear factor-κB (p-NF-κB) p65 protein abundance in the duodenum and jejunum was down-regulated (P < 0.05) following AOS supplementation. According to the above results, the enhanced intestinal integrity in AOS-supplemented pigs appears to be associated with the elevated antioxidant capacity and the reduced mast cell degranulation, as well as the inhibited pro-inflammatory cytokines production via inhibiting the TLR4/NF-κB and NOD1/NF-κB signalling pathways.

Project description:Hepatic apolipoprotein (apo) B-100 isolated from human plasma is known to contain N-linked oligosaccharides of high-mannose-type and complex-type structures. Sequencing data have revealed that apo B-48 of small-intestinal origin, which represents about 48% of apo B-100 polypeptide from the N-terminus, possesses six potential sites for N-linked oligosaccharides, of which five are likely to be glycosylated. The characterization of the carbohydrate moiety of apo B-48 is the focus of this study. Apo B-48 was labelled with L-[35S]methionine and D-[3H]glucosamine in organ culture of human small-intestinal explants. N-Glycanase treatment resulted in loss of radioactivity from D-[3H]glucosamine-labelled but not L-[35S]methionine-labelled apo B-48 secreted into the medium, and caused no distinct change in mobility of apo B-48 upon electrophoresis on 5% polyacrylamide gel. Analysis of monosaccharide content revealed the presence of 16.8, 17.8, 13.4, 3.4, 2.4 and 2.3 residues of N-acetylglucosamine, mannose, galactose, fucose, xylose and N-acetylgalactosamine respectively. Small-intestinal apo B-48 from human lymph chylomicrons bound to [14C]concanavalin A, and the binding could be inhibited with methyl alpha-D-mannoside. In addition, wheat-germ, peanut, Limulus, soya-bean and Ulex lectins bound apo B-48 specifically. To characterize the carbohydrate moiety further, N-linked oligosaccharides were released by N-Glycanase treatment and reduced with NaB3H4. Labelled oligosaccharides were separated on a concanavalin A-Sepharose column. The majority (78%) were biantennary complex-type structures, 16% were high-mannose type and 6% (not retained by the column) most probably represented higher-branched oligosaccharides. These results suggest the presence of one high-mannose-type and four biantennary complex-type oligosaccharides, as well as probable O-linked sugars in apo B-48. By the use of h.p.l.c., exoglycosidase treatments and ion-exchange chromatography, a mixture of high-mannose-type species with predominant Man8GlcNAc2 as well as monosialylated, desialylated and fucosylated forms of complex-type oligosaccharides were detected.

Project description:Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by weight loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body weight loss and colon shortening of 5-Fu treated mice. In addition, the fecal transplant from 5-Fu treated mice reduced body weight and colon length of vancomycin-pretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathological process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.

Dataset Information

Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.

Publications

Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.

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