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Lactobacillus rhamnosus Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

ABSTRACT: Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties. BALB/c mice were pre-treated with or without LBS via oral gavage, followed by mucositis induction with cisplatin. Our results revealed that the LBS-treated groups significantly attenuated proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α) compared to the CP group. Furthermore, LBS mitigated the damaged tight junction integrity caused by CP via up-regulating the levels of claudin, occludin, ZO-1, and mucin-2 protein (MUC-2). Finally, the 16S rRNA fecal microbiome genomic analysis showed that LBS administration enhanced the growth of beneficial bacteria, i.e., Firmicutes and Lachnospiraceae, while the relative abundance of the opportunistic bacteria Bacteroides and Proteobacteria decreased. Collectively, LBS was found to beneficially modulate microbial composition structure and functions and enrich the ecological diversity in the gut.

SUBMITTER: Alsholi DM

PROVIDER: S-EPMC10674506 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Lactobacillus rhamnosus Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

Alsholi Duaa M DM Yacoub Ghazi Suleiman GS Rehman Ata Ur AU Ullah Hidayat H Khan Asif Iqbal AI Deng Ting T Siddiqui Nimra Zafar NZ Alioui Yamina Y Farooqui Nabeel Ahmed NA Elkharti Maroua M Li Yanxia Y Wang Liang L Xin Yi Y

Pathogens (Basel, Switzerland) 20231111 11

Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties ...[more]

PMID: 38003804

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Project description:BackgroundThere are close links between chemotherapy-induced intestinal mucositis and microbiota dysbiosis. Previous studies indicated that D-methionine was an excellent candidate for a chemopreventive agent. Here, we investigated the effects of D-methionine on cisplatin-induced mucositis.Materials and methodsMale Wistar rats (176-200 g, 6 weeks old) were given cisplatin (5 mg/kg) and treated with D-methionine (300 mg/kg). Histopathological, digestive enzymes activity, oxidative/antioxidant status, proinflammatory/anti-inflammatory cytokines in intestinal tissues were measured. Next-generation sequencing technologies were also performed to investigate the gut microbial ecology.ResultsD-methionine administration increased villus length and crypt depth and improved digestive enzyme (leucine aminopeptidase, sucrose and alkaline phosphatase) activities in the brush-border membrane of cisplatin-treated rats (p < 0.05). Furthermore, D-methionine significantly attenuated oxidative stress and inflammatory reaction and increased interleukin-10 levels in cisplatin-induced intestinal mucositis (p < 0.05). Cisplatin administration resulted in high relative abundances of Deferribacteres and Proteobacteria and a low diversity of the microbiota when compared with control groups, D-methionine only and cisplatin plus D-methionine. Cisplatin markedly increased comparative abundances of Bacteroides caccae, Escherichia coli, Mucispirillum schaedleri, Bacteroides uniformis and Desulfovibrio C21-c20, while Lactobacillus was almost completely depleted, compared with the control group. There were higher abundances of Lactobacillus, Lachnospiraceae, and Clostridium butyrium in cisplatin plus D-methionine rats than in cisplatin rats. D-methionine treatment alone significantly increased the number of Lactobacillus reuteri.ConclusionD-methionine protects against cisplatin-induced intestinal damage through antioxidative and anti-inflammatory effects. By enhancing growth of beneficial bacteria (Lachnospiraceae and Lactobacillus), D-methionine attenuates gut microbiome imbalance caused by cisplatin and maintains gut homeostasis.

Project description:Weaning disturbs the intestinal barrier function and increases the risk of infection in piglets. Probiotics exert beneficial health effects, mainly by reinforcing the intestinal epithelium and modulating the gut microbiota. However, the mechanisms of action, and especially, the specific regulatory effects of modulated microbiota by probiotics on the intestinal epithelium have not yet been elucidated. The present study aimed to decipher the protective effects of the probiotic Lactobacillus plantarum strain ZLP001 on the intestinal epithelium and microbiota as well as the effects of modulated microbiota on epithelial function. Paracellular permeability was measured with fluorescein isothiocyanate-dextran (FD-4). Gene and protein expression levels of tight junction (TJ) proteins, proinflammatory cytokines, and host defense peptides were determined by RT-qPCR, ELISA, and western blot analysis. Short-chain fatty acid (SCFA) concentrations were measured by ion chromatography. Fecal microbiota composition was assessed by high-throughput sequencing. The results showed that pretreatment with 108 colony forming units (CFU) mL-1 of L. plantarum ZLP001 significantly counteracted the increase in gut permeability to FD-4 induced by 106 CFU mL-1 enterotoxigenic Escherichia coli (ETEC). In addition, L. plantarum ZLP001 pretreatment alleviated the reduction in TJ proteins (claudin-1, occludin, and ZO-1) and downregulated proinflammatory cytokines IL-6 and IL-8, and TNFα expression and secretion caused by ETEC. L. plantarum ZLP001 also significantly increased the expression of the host defense peptides pBD2 and PG1-5 and pBD2 secretion relative to the control. Furthermore, L. plantarum ZLP001 treatment affected piglet fecal microbiota. The abundance of butyrate-producing bacteria Anaerotruncus and Faecalibacterium was significantly increased in L. plantarum ZLP001-treated piglets, and showed a positive correlation with fecal butyric and acetic acid concentrations. In addition, the cell density of Clostridium sensu stricto 1, which may cause epithelial inflammation, was decreased after L. plantarum ZLP001 administration, while the beneficial Lactobacillus was significantly increased. Our findings suggest that L. plantarum ZLP001 fortifies the intestinal barrier by strengthening epithelial defense functions and modulating gut microbiota.

Dataset Information

Lactobacillus rhamnosus Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

Publications

<i>Lactobacillus rhamnosus</i> Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

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