Carbohydrate-active enzymes (CAZymes) in the gut microbiome

Wardman, Jacob F.; Bains, Rajneesh K.; Rahfeld, Peter; Withers, Stephen G.

doi:10.1038/s41579-022-00712-1

Cited by 272 publications

(133 citation statements)

References 170 publications

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“…To investigate the glycan utilization potential of Tmu and Tc, we used dbCAN2 to identify CAZymes in the protist transcriptomes (Zhang et al, 2018). Consistent with Tc fermenting mucus glycans, we identified highly expressed CAZymes with putative mucolytic activity in Tc (Figure 4F) (Lombard et al, 2014;Smits et al, 2017;Wardman et al, 2022). Tc expresses CAZymes with predicted activity against all of the sugar subunits found on mucus glycans, and these CAZymes are members of Glycoside Hydrolase (GH) families associated with mucus degradation (Figure 4F) (Desai et al, 2016;Smits et al, 2017).…”

Section: Tmu and Tc Occupy Different Nutritional Niches Within The Mi...mentioning

confidence: 96%

Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition

Gerrick

West

Mechler

et al. 2022

Preprint

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Protists in the gut microbiota influence intestinal immunity and epithelial composition, yet the mechanisms used by these protists to shape the gut environment remain poorly understood. Here, we identify a new protist species, Tritrichomonas casperi, and show that metabolic differences between closely related commensal protists modulate their effects on host immunity and determine their ecological niche within the murine microbiota. Genomic and metabolomic analysis of commensal tritrichomonads reveal species-level differences in excretion of the tuft cell activating metabolite succinate, leading to differential induction of Th1, Th2, and Th17 cells in the small intestine. Using defined diets and in vitro growth assays, we show that different tritrichomonad species preferentially rely on dietary polysaccharides or mucus glycans, which leads to trans-kingdom competition with specific bacteria in the microbiota. Our findings elucidate differences in commensal tritrichomonad metabolism and suggest how dietary interventions could regulate the impact of these protists on gut health.

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Section: Tmu and Tc Occupy Different Nutritional Niches Within The Mi...mentioning

confidence: 96%

Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition

Gerrick

West

Mechler

et al. 2022

Preprint

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“…The higher the weight w i is, the more important the gene i is. (4) According to Equation 4, the constrained optimization problem becomes as shown from Equation 5when |v| > r. Otherwise, the optimization problem becomes as in Equation 6. Depending on the dataset, this leads to different cost functions and different weights as a result, when compared to the original SVM in Section 2.1.…”

Section: Computational Frameworkmentioning

confidence: 99%

“…As carbohydrates break down into glucose and enter the blood stream, beta cells secrete insulin to absorb glucose into cells for energy. Insulin mainly aims to store excess glucose in the liver [4][5][6]. When beta cells do not function properly, insulin is not secreted and blood glucose levels are elevated.…”

Section: Introductionmentioning

confidence: 99%

A new machine learning based computational framework identifies therapeutic targets and unveils influential genes in pancreatic islet cells

Turki

Taguchi

2022

Preprint

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Pancreatic islets comprise a group of cells that produce hormones regulating blood glucose levels. Particularly, the alpha and beta islet cells produce glucagon and insulin to stabilize blood glucose. When beta islet cells are dysfunctional, insulin is not secreted, inducing a glucose metabolic disorder. Identifying effective therapeutic targets against the disease is a complicated task and is yet not conclusive. To close the wide gap between understanding the molecular mechanism of pancreatic islet cells and providing effective therapeutic targets, we present a computational framework to identify potential therapeutic targets against pancreatic disorders. First, we downloaded three transcriptome expression profiling datasets pertaining to pancreatic islet cells (GSE87375, GSE79457, GSE110154) from the Gene Expression Omnibus database. For each dataset, we extracted expression profiles for two cell types. We then provided the extracted expression profile along with the cell types to our proposed constrained optimization problem of a support vector machine and to other existing methods, selecting important genes from the expression profiles. Finally, we performed (1) an evaluation from a classification perspective showing the superiority of our methods against the baseline; and (2) an enrichment analysis showing that our methods achieved better outcomes. Results for the three datasets included 44 unique genes and 10 unique transcription factors (SP1, HDAC1, EGR1, E2F1, AR, STAT6, RELA, SP3, NFKB1, and ESR1) that have been reported related to pancreatic islet functions, diseases, and therapeutic targets.

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“…Resident microbes alter mucin’s glycan composition and stimulate its secretion (Arike et al, 2017; Bates et al, 2006; Bergstrom et al, 2020; Pickard et al, 2014). Additionally, microbes encode glycoside hydrolase (GH) enzymes that process glycan O-linkages on mucin, releasing energy-rich monomeric and multimeric glycan products that can also serve as molecular signals to microbiota (Crouch et al, 2020; Koropatkin et al, 2012; Ndeh & Gilbert, 2018; Wang et al, 2020; Wardman et al, 2022). The mechanisms through which mucin glycans may signal to microbiota members and whether these processes impact symbiosis remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

A mucin-regulated adhesin determines the intestinal biogeography and inflammatory character of a bacterial symbiont

Smith

Sundarraman

Melançon

et al. 2022

Preprint

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In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but also provides glycan cues that regulate microbial behaviors. Using experimental evolution, we discovered a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates expression of a mucin-binding adhesin we named MbpA. When MbpA is disrupted, Aer01 colonizes to normal levels, but is largely planktonic and elicits increased intestinal inflammation, traits which are reversed by increasing cell surface MpbA. MbpA-like adhesins are common in human-associated bacteria and expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restored lumenal aggregation and reversed its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.

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Carbohydrate-active enzymes (CAZymes) in the gut microbiome

Cited by 272 publications

References 170 publications

Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition

Metabolic diversity in commensal protists regulates intestinal immunity and trans-kingdom competition

A new machine learning based computational framework identifies therapeutic targets and unveils influential genes in pancreatic islet cells

A mucin-regulated adhesin determines the intestinal biogeography and inflammatory character of a bacterial symbiont

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