Desulfovibrio in the Gut: The Enemy within?

Singh, Sudha; Carroll‐Portillo, Amanda; Lin, Henry C.

doi:10.3390/microorganisms11071772

Cited by 31 publications

(19 citation statements)

References 193 publications

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“…Independent of these covariates, several gut bacterial genera enriched in individuals with lower BMFs (CORNCOB, p < 0.001), such as Christensenellaceae_R-7_group , Anaerotruncus , Blautia , Family_XIII_AD3011_group (Anaerovoracaceae family), and Methanobrevibacter , were previously found to be enriched in Parkinson’s disease (PD) patients who often suffer from chronic constipation 44 . Desulfovibrio , which has been shown to be enriched in several disease states 45 , was elevated at lower BMF ( Fig. 4 ).…”

Section: Discussionmentioning

confidence: 89%

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

Johnson

Diener

Levine

et al. 2023

Preprint

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ObiectiveBowel movement frequency (BMF) variation has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Slow intestinal transit times (constipation) are thought to lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, these phenomena have not been characterized in generally-healthy populations, and the connections between microbial metabolism and the early-stage development and progression of chronic disease remain underexplored.DesignHere, we examine the phenotypic impact of BMF variation across a cohort of over 2,000 generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data.ResultsWe show significant differences in key blood plasma metabolites, proteins, chemistries, gut bacterial genera, and lifestyle factors across BMF groups that have been linked, in particular, to inflammation and CKD severity and progression.DiscussionIn addition to dissecting BMF-related heterogeneity in blood metabolites, proteins, and the gut microbiome, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which suggest several potential strategies for mitigating constipation and diarrhea. Overall, this work highlights the potential for managing BMF to prevent disease.What is already known about this topicConstipation and diarrhea are linked to several chronic diseases, like IBD, CKD, and neurodegenerative disorders. Chronic constipation, in particular, is associated with the increased production of microbially-derived uremic toxins in the gut due to an ecosystem-wide switch from fiber fermentation to protein fermentation. A build-up of these gut-derived toxins in blood, like p-cresol, has been associated with CKD disease progression and severity.What this study addsWhile prior work has demonstrated associations between microbially-derived uremic toxins, constipation, and CKD severity/progression, here we show similar signatures in a generally-healthy cohort. Overall, we map out the molecular phenotypic effects of aberrant BMFs across individuals without any apparent disease, and show how these effects precede, and may contribute to, the development of chronic disease. We find that certain lifestyle and dietary patterns, like higher levels of exercise, reduced anxiety levels, a more plant-based diet, and drinking more water, are associated with a more optimal BMF range.How this study might affect research, policy, or practiceOverall, we suggest that even mild levels of chronic constipation may cause damage to organ systems over time and ultimately give rise to chronic diseases, like CKD or neurodegeneration. These findings pave the way for future research into early interventions for individuals at risk of developing chronic diseases related to BMF abnormalities. Managing BMF abnormalities prior to disease development may be an important disease prevention strategy, but this will require further evidence through longitudinal human intervention trials.

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Section: Discussionmentioning

confidence: 89%

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

Johnson

Diener

Levine

et al. 2023

Preprint

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“…Bacteria having the highest SHAP values when using any model with PA were probiotic candidates such as Akkermansia municiphila (Cani et al 2022) and potantially beneficial microbes such as Firmicutes bacterium CAG:95 and Firmicutes bacterium CAG:110 (Zeybel et al 2022). Models using PA as data transformation assigned also higher SHAP values to opportunistic pathobionts such as Desulfovibrio piger (Singh, Carroll-Portillo, and Lin 2023) , Fusobacterium nucleatum (Brennan and Garrett 2019) and Erysipelatoclostridium ramosum (previously known as Clostridium ramosum ) (Bojović et al 2020). This observation further highlights the difference in the biomarker profiles informed by different data transformations.…”

Section: Resultsmentioning

confidence: 99%

Effects of Data Transformation and Model Selection on Feature Importance in Microbiome Classification Data

Karwowska,

Aasmets,

Kosciolek

et al. 2023

Preprint

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Accurate classification of host phenotypes from microbiome data is essential for future therapies in microbiome-based medicine and machine learning approaches have proved to be an effective solution for the task. The complex nature of the gut microbiome, data sparsity, compositionality and population-specificity however remain challenging, which highlights the critical need for standardized methodologies to improve the accuracy and reproducibility of the results. Microbiome data transformations can alleviate some of the aforementioned challenges, but their usage in machine learning tasks has largely been unexplored. Our aim was to assess the impact of various data transformations on the accuracy, generalizability and feature selection by analysis using more than 8,500 samples from 24 shotgun metagenomic datasets. Our findings demonstrate the feasibility of distinguishing between healthy and diseased individuals using microbiome data with minimal dependence on the algorithm and transformation selection. Remarkably, presence-absence transformation performed comparably well to abundance-based transformations, and only a small subset of predictors is crucial for accurate classification. However, while different transformations resulted in comparable classification performance, the most important features varied significantly, which highlight the need to reevaluate machine-learning based biomarker detection. Our research provides valuable guidance for applying machine learning on microbiome data, offering novel insights and highlighting important areas for future research.

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“…Studies have shown that Odoribacter effectively alleviates colitis in mice through a mechanism that may be related to the regulation of neutrophil extracellular trap formation [ 44 ]. Desulfovibrio is a phylotype related to hydrogen-scavenging and sulfate reduction [ 45 ] and has been implicated in a variety of diseases, but its relationship with IBD remains controversial, and related research results are conflicting [ 46 ]. However, studies have shown that Desulfovibrio may be effective in attenuating liver damage by producing acetic acid and regulating hepatic lipid metabolism in mice [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

S/O/W Emulsion with CAPE Ameliorates DSS-Induced Colitis by Regulating NF-κB Pathway, Gut Microbiota and Fecal Metabolome in C57BL/6 Mice

Wei,

Dai,

Liu

et al. 2024

Nutrients

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Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.

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Desulfovibrio in the Gut: The Enemy within?

Cited by 31 publications

References 193 publications

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

Effects of Data Transformation and Model Selection on Feature Importance in Microbiome Classification Data

S/O/W Emulsion with CAPE Ameliorates DSS-Induced Colitis by Regulating NF-κB Pathway, Gut Microbiota and Fecal Metabolome in C57BL/6 Mice

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