Effects Of Xylooligosaccharide On Improving Quality Of Life In Colorectal Cancer Patients Receiving Chemotherapy By Regulating Gut Microbiota

Colorectal cancer(CRC)is the third most common cancer worldwide.Recent studies on the associations between gut microbiota and CRC have provided new ideas to elucidate the pathogenesis of CRC.However,the findings of previous studies have not uniform nor conclusive.These variances may be related to differences in primary tumor sites,sampling sites,and stages of the disease,which have posed opportunities and challenges to the diagnosis and treatment of CRC.Currently,the high incidence of adverse effects of CRC chemotherapy seriously affects the quality of life of patients.Therefore,it is particularly urgent to find safe and effective methods for addressing these problems.Numerous studies have shown that prebiotics could reduce the adverse effects of chemotherapy for CRC patients by modulating gut microbiota.As a prebiotic,xylooligosaccharide(XOS)has the potential to improve the efficacy and adverse effects of chemotherapy on patients by regulating gut microbiota,improving immune response,and protecting the intestinal barrier.Here,we used 16 S r RNA gene sequencing technology to compare the differences in the gut microbiota of CRC patients between different mucosa samples and between mucosa and fecal samples,and further grouped the samples according to primary tumor sites,disease stages,and fecal occult blood test results to analyse the distribution characteristics of gut microbiota of CRC patients from multiple perspectives.Moreover,we explored the effects of XOS on improving chemotherapy response in CRC patients by regulating gut microbiota,providing a basis for the development of personalized cancer adjuvant nutrition therapy.The main findings were as follows:Firstly,the microbial compositions of CRC patients were explored by collecting tumor mucosa,para-cancerous mucosa,normal mucosa,and fecal samples from 98 patients.From the comparison of tumor and normal mucosal microbiota and the comparison of three types of mucosal and fecal microbiota,we identified 6 key genera by LEf Se analysis including Fusobacterium,Gemella,Campylobacter,Peptostreptococcus,Alloprevotella,and Parvimonas.Among them,Fusobacterium,Gemella,and Campylobacter were the dominant genera in tumor mucosa.These genera were also reported to be frequently detected in the oral cavity.Porphyromonas and Haemophilus were the key genera in left-and right-sided CRC patients,respectively.Prevotella was highly enriched in the intestine of patients with stage I CRC and decreased in abundance with disease progression.Collinsella,Eubacterium hallii group,and Colidextribacter were key genera in patients with positive fecal occult blood tests,whereas Holdemanella was the key genus in patients with negative fecal occult blood tests.Subsequently,to evaluate the effects of XOS intervention on CRC patients during chemotherapy,patients receiving XELOX regimen(oxaliplatin and capecitabine)and FOLFOX regimen(5-fluorouracil,leucovorin,and oxaliplatin)were randomly divided into XOS intervention group and blank control group.In terms of gastrointestinal responses,XOS intervention significantly attenuated diarrheal reactions(P<0.05)and showed a tendency to alleviate nausea and vomiting reactions(P=0.055)in patients receiving XELOX regimen.In terms of bone marrow suppressive markers,XOS intervention alleviated the decline in white blood cells(P<0.05),absolute neutrophil counts(P=0.052),and lymphocyte counts(P<0.05)in patients receiving XELOX regimen,and the decline in platelets(P<0.05)in patients receiving FOLFOX regimen.In terms of nutritional markers,XOS significantly increased total protein levels(P<0.05)and tended to increase the albumin levels(P=0.073)in patients receiving FOLFOX regimen.In addition,XOS tended to improve inflammatory responses(P>0.05)in patients receiving FOLFOX regimen,significantly reduced CA19-9 levels(P<0.05)in patients receiving XELOX regimen,and tended to increase plasma concentrations of capecitabine and fluorouracil(P>0.05).XOS did not have a significant effect on fecal short-chain fatty acids(SCFAs)levels(P>0.05).Finally,the effects of XOS on the gut microbiota of CRC patients were explored.Compared to control group,XOS enriched Dialister and Intestinibacter and inhibited the abundance of Fusobacterium in patients receiving XELOX regimen.XOS enriched Bifidobacterium,Roseburia,Parabacteroides,and Dorea and inhibited the abundance of Enterobacter and Hungatella in patients receiving FOLFOX regimen.We hypothesized that XOS may exert beneficial effects on patients by enriching beneficial bacteria and inhibiting opportunistic pathogenic bacteria,especially Fusobacterium.The PICRUSt prediction revealed that XOS could upregulate thiamine metabolism(ko00730),fatty acid biosynthesis(ko00061),and steroid biosynthesis(ko00100)pathways,and downregulate lysine degradation(k000310),fatty acid degradation(ko00071),valine,leucine,and isoleucine degradation(ko00280)pathways.XOS could upregulate the thiamine metabolism(ko00730)pathway and the adenylate kinase that catalyzes thiamine diphosphate to thiamine triphosphate on this pathway.Thiamine absorption has been reported to be closely related to nutritional status.We speculate from the experimental results that XOS could relieve diarrhea symptoms,promote thiamine absorption,and upregulate thiamine metabolic pathway,thereby improving the nutritional status of patients.Correlation analysis of the abundance of the differential genera with clinical indicators revealed that in terms of blood indicators,XOS-enriched Dialister was significantly positively correlated with neutrophil counts(P<0.05),Bifidobacterium was significantly positively correlated with lymphocyte counts(P<0.05),and Dorea was significantly positively correlated with white blood cells and lymphocyte counts(P<0.01).Fusobacterium inhibited by XOS was significantly negatively correlated with hemoglobin,neutrophil counts,and albumin(P<0.05).In terms of SCFAs,XOS-enriched Dialister(P>0.05),Roseburia(P<0.05),Bifidobacterium(P<0.01),and Dorea(P<0.05)were all positively correlated with butyrate and isobutyric acid levels.It was further demonstrated that XOS caused the alteration of related indicators by regulating gut microbiota.Overall,this study analyzed the gut microbiota characteristics of CRC patients from multiple perspectives and found that Fusobacterium was enriched in tumor mucosa and closely associated with positive fecal occult blood results,implying that Fusobacterium plays an essential role in CRC development.XOS could enrich beneficial genera,inhibit the abundance of opportunistic pathogenic bacteria such as Fusobacterium,alleviate the adverse effects of chemotherapy,and improve nutrition levels and quality of life in CRC patients.The above results provide ideas for the further development of personalized and precise adjuvant nutritional therapy for cancer based on gut microbiota.