Dataset Information

Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients.

ABSTRACT: Lynch syndrome (LS) is a dominantly inherited condition with incomplete penetrance, characterized by high predisposition to colorectal cancer (CRC), endometrial and ovarian cancers, as well as to other tumors. LS is associated with constitutive DNA mismatch repair (MMR) gene defects, and carriers of the same pathogenic variants can show great phenotypic heterogeneity in terms of cancer spectrum. In the last years, human gut microbiota got a foothold among risk factors responsible for the onset and evolution of sporadic CRC, but its possible involvement in the modulation of LS patients' phenotype still needs to be investigated. In this pilot study, we performed 16S rRNA gene sequencing of bacterial DNA extracted from fecal samples of 10 postoperative LS female patients who had developed colonic lesions (L-CRC) or gynecological cancers (L-GC). Our preliminary data show no differences between microbial communities of L-CRC and L-GC patients, but they plant the seed of the possible existence of a fecal microbiota pattern associated with LS genetic background, with Faecalibacterium prausnitzii, Parabacteroides distasonis, Ruminococcus bromii, Bacteroides plebeius, Bacteroides fragilis and Bacteroides uniformis species being the most significantly over-represented in LS patients (comprising both L-CRC and L-GC groups) compared to healthy subjects.

SUBMITTER: Mori G

PROVIDER: S-EPMC6682596 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients.

Mori Giorgia G Orena Beatrice Silvia BS Cultrera Ilenia I Barbieri Giulia G Albertini Alessandra M AM Ranzani Guglielmina Nadia GN Carnevali Ileana I Tibiletti Maria Grazia MG Pasca Maria Rosalia MR

Frontiers in microbiology 20190730

Lynch syndrome (LS) is a dominantly inherited condition with incomplete penetrance, characterized by high predisposition to colorectal cancer (CRC), endometrial and ovarian cancers, as well as to other tumors. LS is associated with constitutive DNA mismatch repair (MMR) gene defects, and carriers of the same pathogenic variants can show great phenotypic heterogeneity in terms of cancer spectrum. In the last years, human gut microbiota got a foothold among risk factors responsible for the onset a ...[more]

PMID: 31417532

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Project description:BackgroundLynch syndrome (LS)-associated colorectal cancer (CRC) always ascribes to pathogenic germline mutations in mismatch repair (MMR) genes. However, the penetrance of CRC varies among those with the same MMR gene mutation. Thus, we hypothesized that the gut microbiota is also involved in CRC development in LS families.MethodsThis prospective, observational study was performed from December 2020 to March 2023. We enrolled 72 individuals from 9 LS families across six provinces in China and employed 16S rRNA gene amplicon sequencing to analyze the fecal microbiota components among LS-related CRC patients (AS group), their spouses (BS group), mutation carriers without CRC (CS group), and non-mutation carriers (DS group) using alpha and beta diversity indices.ResultsThere were no apparent differences in age or gender among the four groups. Alpha and beta diversity indices exhibited no significant differences between the AS and BS groups, verifying the role of germline mutations in the occurrence of CRC in LS families. Beta diversity analysis exhibited significant differences between the AS and CS groups, revealing the importance of the gut microbiota for the occurrence of CRC in LS families. A greater difference (both alpha and beta diversity indices) was shown between the AS and DS groups, demonstrating the combined impact of the gut microbiota and genetic germline mutations on the occurrence of CRC in LS families. Compared with those in the CS and DS groups, we identified ten microbial genera enriched in the AS group, and one genus (Bacteroides) decreased in the AS group. Among the elevated genera in the AS group, Agathobacter, Coprococcus and Prevotellaceae_NK3B31_group were butyrate-producing genera.ConclusionThis study found the development of CRC in the LS families can be attributed to the combined effects of gene germline mutations as well as the gut microbiota and provided novel insights into the prevention and treatment of CRC in the LS families.

Project description:IntroductionPost-operative delirium (POD) is a serious complication which occurs after surgery, especially in the elderly undergoing abdominal surgery. Increasing evidence has revealed an association between the gut microbiota and psychological disorders involving the "brain-gut" axis. However, the association between the pathogenesis of POD after abdominal surgery in aging and composition of the gut microbiota remains unclear.MethodsForty patients (≥65 years old) who underwent abdominal surgery were included in the study. Twenty patients had POD, whereas 20 patients did not. POD was diagnosed and assessed using the confusion assessment method (CAM) during the postoperative period. Total DNA fractions were extracted from all fecal samples of patients. 16S rRNA sequencing was performed to determine the composition of the gut microbiota. The quality of the samples was determined by calculating the α- and β-diversities.ResultsThe α- and β-diversities indicated that the samples were eligible for detection and comparison. We observed multiple differentially abundant bacteria in patients with and without POD. Generally, Proteobacteria, Enterbacteriaceae, Escherichia shigella, Klebsiella, Ruminococcus, Roseburia, Blautia, Holdemanella, Anaerostipes, Burkholderiaceae, Peptococcus, Lactobacillus, and Dorea were abundant in the POD cohort, whereas Streptococcus equinus and Blautia hominis were abundant in the control cohort. The results of receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of Escherichia shigella was 0.75. Phenotype prediction showed that the gut microbiota may influence POD by altering the tolerance to oxidative stress.ConclusionThere were significant associations between the pathogenesis of POD and composition of the gut microbiota. Escherichia shigella are promising diagnostic bacterial species for predicting POD onset after abdominal surgery in elderly people.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, Chinese Clinical Trial Registry ChiCTR200030131.

Dataset Information

Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients.

Publications

Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients.

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