Dataset Information

Dietary Efficacy Evaluation by Applying a Prediction Model Using Clinical Fecal Microbiome Data of Colorectal Disease to a Controlled Animal Model from an Obesity Perspective.

ABSTRACT: Obesity associated with a Western diet such as a high-fat diet (HFD) is a known risk factor for inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this study, we aimed to develop fecal microbiome data-based deep learning algorithms for the risk assessment of colorectal diseases. The effects of a HFD and a candidate food (Nypa fruticans, NF) on IBD and CRC risk reduction were also evaluated. Fecal microbiome data were obtained from 109 IBD patients, 111 CRC patients, and 395 healthy control (HC) subjects by 16S rDNA amplicon sequencing. IBD and CRC risk assessment prediction models were then constructed by deep learning algorithms. Dietary effects were evaluated based on fecal microbiome data from rats fed on a regular chow diet (RCD), HFD, and HFD plus ethanol extracts or water extracts of NF. There were significant differences in taxa when IBD and CRC were compared with HC. The diagnostic performance (area under curve, AUC) of the deep learning algorithm was 0.84 for IBD and 0.80 for CRC prediction. Based on the rat fecal microbiome data, IBD and CRC risks were increased in HFD-fed rats versus RCD-fed rats. Interestingly, in the HFD-induced obesity model, the IBD and CRC risk scores were significantly lowered by the administration of ethanol extracts of NF, but not by the administration of water extracts of NF. In conclusion, changes in the fecal microbiome of obesity by Western diet could be important risk factors for the development of IBD and CRC. The risk prediction model developed in this study could be used to evaluate dietary efficacy.

SUBMITTER: Seo H

PROVIDER: S-EPMC9505706 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Dietary Efficacy Evaluation by Applying a Prediction Model Using Clinical Fecal Microbiome Data of Colorectal Disease to a Controlled Animal Model from an Obesity Perspective.

Seo Hochan H Kwon Cheol-O CO Park Joo-Hyun JH Kang Chil-Sung CS Shin Tae-Seop TS Yang Eun-Young EY Jung Jin Woo JW Moon Byoung-Seok BS Kim Yoon-Keun YK

Microorganisms 20220914 9

Obesity associated with a Western diet such as a high-fat diet (HFD) is a known risk factor for inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this study, we aimed to develop fecal microbiome data-based deep learning algorithms for the risk assessment of colorectal diseases. The effects of a HFD and a candidate food (<i>Nypa fruticans</i>, NF) on IBD and CRC risk reduction were also evaluated. Fecal microbiome data were obtained from 109 IBD patients, 111 CRC patients, and 395 ...[more]

PMID: 36144434

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Project description:BackgroundOsteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immune transcriptome in OA pathophysiology.MethodsFeces, peripheral blood mononuclear cells (PBMCs), and SF cells were isolated from healthy skeletally mature horses (n=12; 6 males, 6 females) and those with OA (n=6, 2 females, 4 males). Horses were determined to have OA via lameness evaluation, response to intra-articular (IA) diagnostic analgesia, and radiographic and arthroscopic evidence. Horses were excluded who had received medications or joint injections within 2 months. Cytokine analyses of plasma and SF were performed via multiplex immunoassay. Fecal bacterial microbial 16s DNA sequencing was performed and correlated to bulk RNA sequencing of SF cells and PBMC performed using an Illumina based platform.ResultsHorses with OA had higher body condition scores (P=0.009). Cytokines were elevated in plasma [interleukin (IL)-2, IL-6, IL-18, interferon gamma (IFN-γ), interferon gamma inducible protein 10 (CXCL10 or IP-10), granulocyte colony-stimulating factor (G-CSF)] and SF (IL-1β, IL-6, IL-17A, IL-18, IP-10, G-CSF) in OA. Microbial principal coordinate analysis (PCoA) using Bray-Curtis dissimilarity for β-diversity demonstrated distinct grouping of samples from OA versus healthy horses (P=0.003). Faith alpha diversity was reduced in OA (P=0.02). Analysis of microbiome composition showed differential relative abundance of taxa on multiple levels in OA. Specific phyla (Firmicutes, Verrucomicrobia, Tenericutes, Fibrobacteres), correlated to transcriptomic differences related to cell structure, extracellular matrix, collagen, laminin, migration, and motility, or immune response to inflammation in OA.ConclusionsThese findings provide compelling evidence for a link between obesity, gut microbiome dysbiosis and differential gene expression in distant joint sites associated with development of OA in a relevant large animal model, establishing a connection here that provides a platform from which development of therapeutic interventions targeting the gut microbiome can build.

Project description:Fenbendazole (FBZ) is a common antiparasitic treatment used in research rodent colonies for biosecurity purposes. The effect of this compound has been studied in C57 mice, but never before in a strain of mice that has co-morbidities, such as the blood pressure high (BPH)/5. The BPH/5 mouse is an inbred genetic model of hypertension. While both male and female BPH/5 have high blood pressure, there is a metabolic sexual dimorphism with females displaying key features of obesity. The obese gut microbiome has been linked to hypertension. Therefore, we hypothesized that fenbendazole treatment will alter the gut microbiome in hypertensive mice in a sex dependent manner. To test the influence of FBZ on the BPH/5 gut microbiota, fecal samples were collected pre- and post-treatment from adult BPH/5 mice (males and non-pregnant females). The mice were treated with fenbendazole impregnated feed for five weeks. Post-treatment feces were collected at the end of the treatment period and DNA was extracted, and the V4 region of 16S rRNA was amplified and sequenced using the Illumina MiSeq system. The purpose was to analyze the fecal microbiome before and after FBZ treatment, the results demonstrate changes with treatment in a sex dependent manner. More specifically, differences in community composition were detected in BPH/5 non-pregnant female and males using Bray-Curtis dissimilarity as a measure of beta-diversity (treatment p = 0.002). The ratio of Firmicutes to Bacteroidetes, which has been identified in cases of obesity, was not altered. Yet, Verrucomicrobia was increased in BPH/5 males and females post-treatment and was significantly different by sex (treatment p = 5.85e-05, sex p = 0.0151, and interaction p = 0.045), while Actinobacteria was decreased in the post-treatment mice (treatment p = 0.00017, sex p = 0.5, interaction p = 0.2). These results are indicative of gut dysbiosis compared to pre-treatment controls. Lactobacillus was decreased with FBZ treatment in BPH/5 females only. In conclusion, fenbendazole does alter the gut microbial communities, most notable in the male rather than female BPH/5 mouse. This provides evidence that caution should be taken when providing any gut altering treatments before or during mouse experiments.

Dataset Information

Dietary Efficacy Evaluation by Applying a Prediction Model Using Clinical Fecal Microbiome Data of Colorectal Disease to a Controlled Animal Model from an Obesity Perspective.

Publications

Dietary Efficacy Evaluation by Applying a Prediction Model Using Clinical Fecal Microbiome Data of Colorectal Disease to a Controlled Animal Model from an Obesity Perspective.

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