Dataset Information

Decreased Abundance of Genus Slackia in Individuals With Obesity and Colorectal Adenoma.

ABSTRACT:

Background and aims

The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA.

Methods

This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups.

Results

No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19-10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35-22.0) for genus Slackia and equol reductase-negative participants.

Conclusion

Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

SUBMITTER: Sakai T

PROVIDER: S-EPMC11330935 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decreased Abundance of Genus <i>Slackia</i> in Individuals With Obesity and Colorectal Adenoma.

Sakai Takayuki T Sasaki Yu Y Abe Yasuhiko Y Shoji Masakuni M Nishise Shoichi S Sato Hidenori H Yagi Makoto M Mizumoto Naoko N Onozato Yusuke Y Takashi Kon K Miyano Yuki Y Murakami Ryoko R Umehara Matsuki M Nakamura Shuhei S Ito Minami M Watabe Takahiro T Tsuchiya Hiroko H Goto Hiroki H Miura Takahiro T Sato Ryo R Ueno Yoshiyuki Y

Gastro hep advances 20240311 5

<h4>Background and aims</h4>The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of p ...[more]

PMID: 39165419

Similar Datasets

Project description:BackgroundThe risk of colorectal adenoma (CRA), an important precursor of colorectal cancer, is largely unknown among obese individuals without obesity-related metabolic abnormalities, a condition described as metabolically-healthy obese (MHO). The aim of this study was to examine the association among metabolic status, the different categories of body mass index (BMI), and CRA in a large cohort of adults.MethodsWe analyzed the association among metabolic status, BMI categories and CRA in asymptomatic adults who underwent a first-time colonoscopy as part of the comprehensive health check-up program at the Health Promotion Center of Samsung Medical Center, from January 2005 to December 2012. Being metabolically healthy was defined as lacking any metabolic syndrome components and having a homeostasis model assessment of insulin resistance <2.5.ResultsThe prevalence of "any," "multiple," and "high-risk" CRA was 25.6%, 8.3%, and 4.4% among 9,182 metabolically-healthy participants, and 35.9%, 12.5%, and 7.0% among 17,407 metabolically-unhealthy participants, respectively. Increased BMI showed a significant dose-dependent relationship with the prevalence of "any," "multiple," and "high-risk" CRA, in both metabolically-healthy and unhealthy participants. In multivariable-adjusted models that accounted for potential confounders including age, sex, smoking, alcohol, first-degree family history of colorectal cancer, and aspirin use, the odds ratio (OR) for any CRA comparing MHO with metabolically-healthy normal-weight (MHNW) participants was 1.25 (95% confidence interval (CI), 1.09-1.43). Further adjustment for metabolic components associated with obesity did not significantly change the association. Similarly, the ORs for multiple CRAs and high risk CRA were higher in MHO participants than MHNW participants [ORs (95% CI), 1.63 (1.31-2.04) and 1.53 (1.14-2.04), respectively].ConclusionsThe MHO phenotype was closely associated with higher prevalence of CRA, including high-risk adenoma. This finding supports the conclusion that MHO increases the risk of colorectal cancer.

Project description:BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy obese (MHO; n = 15), and metabolically unhealthy obese (MUO; n = 20).RESULTSAT pO2 progressively declined from the MHL to the MHO to the MUO group, and was positively associated with hepatic and whole-body insulin sensitivity. AT pO2 was positively associated with the expression of genes involved in BCAA catabolism, in conjunction with an inverse relationship between AT pO2 and plasma BCAA concentrations. AT pO2 was negatively associated with AT gene expression of markers of inflammation and fibrosis. Plasma PAI-1 increased from the MHL to the MHO to the MUO group and was negatively correlated with AT pO2, whereas the plasma concentrations of other cytokines and chemokines were not different among the MHL and MUO groups.CONCLUSIONThese results support the notion that reduced AT oxygenation in individuals with obesity contributes to insulin resistance by increasing plasma PAI-1 concentrations and decreasing AT BCAA catabolism and thereby increasing plasma BCAA concentrations.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants K01DK109119, T32HL130357, K01DK116917, R01ES027595, P42ES010337, DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK052574 (Digestive Disease Research Center), and UL1TR002345 (Clinical and Translational Science Award); NIH Shared Instrumentation Grants S10RR0227552, S10OD020025, and S10OD026929; and the Foundation for Barnes-Jewish Hospital.

Project description:BackgroundColorectal cancer (CRC) development is accompanied by changes in expression for several genes; but the details of the underlying regulatory procesess remain unknown. Our aims were to assess the role of epigenetic processes in tumour formation and to identify characteristic DNA methylation and miRNA alterations in the colorectal adenoma-carcinoma sequence.MethodsWhole genome expression profiling was performed on colonic biopsy samples (49 healthy normal, 49 colorectal adenoma (AD), 49 CRC); on laser capture microdissected (LCM) epithelial and stromal cells from 6 CRC-normal adjacent tissue (NAT) samples pairs, and on demethylated human CRC cell lines using HGU133 Plus 2.0 microarrays (Affymetrix). Methylation status of genes with gradually altering expression along the AD-CRC sequence was further analysed on 10-10 macrodissected and 5-5 LCM samples from healthy colon, from adenoma and from CRC biopsy samples using bisulfite-sequencing PCR (BS-PCR) followed by pyrosequencing. In silico miRNA prediction for the selected genes was performed with miRWALK algorithm, miRNA expression was analysed on 3 CRC-NAT sample pairs and 3 adenoma tissue samples using the Human Panel I + II (Exiqon). SFRP1 immunohistochemistry experiments were performed.ResultsA set of transcripts (18 genes including MAL, SFRP1, SULT1A1, PRIMA1, PTGDR) showed decreasing expression (p < 0.01) in the biopsy samples along the adenoma-carcinoma sequence. Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g. BCL2, MAL, PTGS2). Demethylation treatment could upregulate gene expression of genes that were found to be hypermethylated in human CRC tissue samples. Decreasing protein levels of SFRP1 was also observed along the adenoma-carcinoma sequence.ConclusionHypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer.