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Despite ongoing breakthroughs in novel anticancer therapies, chemotherapy remains a mainstream therapeutic modality in different types of cancer. Unfortunately, chemotherapy-related toxicity (CRT) often leads to dose limitation, and even results in treatment termination. Over the past few years, accumulating evidence has indicated that the gut microbiota is extensively engaged in various toxicities initiated by chemotherapeutic drugs, either directly or indirectly. The gut microbiota can now be targeted to reduce the toxicity of chemotherapy. In the current review, we summarized the clinical relationship between the gut microbiota and CRT, as well as the critical role of the gut microbiota in the occurrence and development of CRT. We then summarized the key mechanisms by which the gut microbiota modulates CRT. Furthermore, currently available strategies to mitigate CRT by targeting the gut microbiota were summarized and discussed. This review offers a novel perspective for the mitigation of diverse chemotherapy-associated toxic reactions in cancer patients and the future development of innovative drugs or functional supplements to alleviate CRT via targeting the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Dysregulation in gut microbiota and host cometabolome contributes to the complicated pathology of ulcerative colitis (UC), while Zuo-Jin-Wan (ZJW), a traditional Chinese medicine has shown therapeutic effects against UC with its underlying mechanism remains elusive.Purpose: This study utilized an integrated analysis combining gut microbiome and host cometabolism to disclose the potential therapeutic mechanism of ZJW on dextran sulfate sodium (DSS)-induced UC in rats.Methods: We first evaluated the therapeutic effects of ZJW treatment in DSS-induced rat model. 16S rRNA sequencing, 1H NMR spectroscopy-based metabolomics and Spearman correlation analysis were conducted to explore the potential therapeutic mechanism during the treatment.Results: Our results showed that UC symptoms in ZJW rats were significantly attenuated. Marked decline in microbial diversity in ZJW group was accompanied by its correspondent function adjustment. Specific enrichment of genus Bacteroides, Sutterella, Akkermansia and Roseburia along with the major varying amino acid metabolism and lipid metabolism were observed meantime. Metabolic data further corroborated that ZJW-related metabolic changes were basically gathered in amino acid metabolism, carbohydrate/energy metabolism and lipid metabolism. Of note, some biochemical parameters were deeply implicated with the discriminative microbial genera and metabolites involved in tricarboxylic acid (TCA) cycle and amino acid metabolism, indicating the microbiome-metabolome association in gut microbiota-metabolite-phenotype axis during UC treatment of ZJW.Conclusion: For the first time, integrated microbiome-metabolome analysis depicted that ZJW could alleviate DSS-induced UC in rats via a crosstalk between gut microbiota and host cometabolites. [ABSTRACT FROM AUTHOR]

Capsular polysaccharides derived from Bacteroides species have emerged as potential mitigators of intestinal inflammation in murine models. However, research on capsular polysaccharides from B. uniformis , a Bacteroides species with reduced abundance in colons of patients with ulcerative colitis, remains scarce. In this study, we extracted a neutral polysaccharide component from B. uniformis ATCC8492, termed BUCPS1B, using ultrasonic disruption, ethanol precipitation, and anion exchange chromatography. Structural characterization revealed BUCPS1B as a water-soluble polysaccharide with an α-1,4-glucan main chain adorned with minor substituent sugar residues. BUCPS1B alleviated intestinal inflammation in a mouse model of colitis and induced polarization of macrophages into M2-type. Furthermore, BUCPS1B modulated the gut microbiota composition, increased the abundance of the probiotic Akkermansia muciniphila and altered the gut metabolic profile to promote phenylalanine and short chain fatty acids metabolism. BUCPS1B is therefore a promising candidate to prevent inflammation and augment intestinal health. [ABSTRACT FROM AUTHOR]

• Gallic acid (GA) alleviates UC and increase the group 3 innate lymphoid cells (ILC3) numbers in a manner dependent on the microbiota. • GA treatment regulate the mouse gut microbial community, and alters the diversity of intestinal microbes. • Treatment of GA regulate bile acid metabolism, leading to the production of UDCA, isoalloLCA, and 3-oxoLCA. • Treatment of bile acids UDCA, isoalloLCA, and 3-oxoLCA promote ILC3 numbers. Gallic acid (GA), a plant phenol that is widely distributed in fruits and vegetables, and exhibits a protective role against ulcerative colitis (UC). UC is an inflammatory disease characterized by immune response disorders. However, the role and mechanism of action of GA in gut immunity remain unknown. Here, we observed that GA treatment improved enteritis symptoms, decreased the concentrations of cytokines TNF-α, IFN-γ, IL-6, IL-17A, and IL-23, increased the concentrations of cytokines IL-10, TGF-β and IL-22, and increased the proportion of group 3 innate lymphoid cells (ILC3) in mesenteric lymph nodes and lamina propria. However, GA did not upregulate ILC3 or impair UC in antibody-treated sterile mice. Notably, transplantation of fecal bacteria derived from GA-treated UC mice, instead of UC mice, increased ILC3 levels. Therefore, we analyzed the gut microbiota and related metabolites to elucidate the mechanism promoting ILC3. We determined that GA treatment altered the diversity of the gut microbiota and activated the bile acid (BA) metabolic pathway. We evaluated three BAs, namely, UDCA, isoalloLCA, and 3-oxoLCA that were significantly upregulated after GA treatment, improved UC symptoms, and elevated the proportion of ILC3 in vivo and in vitro. Collectively, these data indicate that GA attenuates UC by elevating ILC3 proportion, regulating the gut microbiota, and impacting BA metabolism. Additionally, we highlight the modulatory effects of BAs on ILC3 for the first time. Our findings provide novel insights into the multiple roles of GA in alleviating UC and provide a mechanistic explanation that supports the dietary nutrition in UC therapy. Gallic acid (GA) attenuates ulcerative colitis (UC) by elevating ILC3 proportion, regulating the gut microbiota, and impacting BA metabolism, such as UDCA, isoalloILCA and 3-oxoLCA. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Synbiotic effectively ameliorates constipation symptoms in rats. • Synbiotic increases relative abundances of Lactobacillus and Faecalibaculum in constipated rats. • Synbiotic improves serum excitatory neurotransmitter levels in constipated rats. • Synbiotic promotes fecal propionate and butyrate production in constipation rats. • Synbiotic inhibits inflammatory responses in constipated rats. The purpose of this study is to investigate the mitigatory effect of a novel synbiotic (SBT) on constipation from the perspective of gut microbiome and metabolome. Here, intake of SBT effectively attenuated diphenoxylate-induced constipation, recuperated colonic epithelial integrity and increased serum levels of gastrointestinal excitatory neurotransmitters (P substance, vasoactive intestinal peptide, motilin, gastrin and serotonin). 16S rRNA sequencing showed that SBT intake rehabilitated the composition and functionality of gut microbiota. Relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Lactobacillus , Faecalibaculum and Bifidobacterium were elevated by administration of SBT. The gas chromatography-mass spectrometry analysis confirmed that fecal concentrations of propionate and butyrate were significantly increased in the rats intervened with SBT. In addition, SBT ingestion reduced the relative levels of opportunistic pathogens, such as Oscillibacter , Parasutterella and Parabacteroides. Microbial functional prediction showed that the relative abundances of lipopolysaccharide (LPS) biosynthesis and arachidonic acid metabolism were downregulated with SBT administration, which were in accordance with the serum metabolomics results. Furthermore, serum levels of LPS, tumour necrosis factor alpha and interleukin 6 were significantly decreased, indicating that SBT supplementation suppressed inflammatory responses. Therefore, this study demonstrated that consumption of SBT ameliorated constipation possibly by regulating gut microbiota, promoting the SCFAs production and inhibiting inflammatory responses in rats. Our study also indicated that SBT may provide a novel alternative strategy for the treatment of constipation clinically in future. [ABSTRACT FROM AUTHOR]