Stool multi-omics for the study of host–microbe interactions in inflammatory bowel disease

Sauceda, Consuelo; Bayne, Charlie; Sudqi, Khadijeh; González, Antonio; Dulai, Parambir S.; Knight, Rob; Gonzalez, David J.; González, Carlos Gutiérrez

doi:10.1080/19490976.2022.2154092

Cited by 11 publications

(6 citation statements)

References 125 publications

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“…Many disease states have associated host-microbe interactions that may influence pathogenesis (69,70). At this time, clinical benefits of microbial manipulation are limited to CDI.…”

Section: Discussionmentioning

confidence: 99%

The Gut Microbiome: A Primer for the Clinician

Aroniadis,

Grinspan

2024

Am J Gastroenterol

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“…Many disease states have associated host-microbe interactions that may influence pathogenesis (69,70). At this time, clinical benefits of microbial manipulation are limited to CDI.…”

Section: Discussionmentioning

confidence: 99%

The Gut Microbiome: A Primer for the Clinician

Aroniadis,

Grinspan

2024

Am J Gastroenterol

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“…17 The other key component that plays a role in IBD pathogenesis is the environment. 18 19 Specifically, diet, vitamin D deficiency, exposure to antibiotics, and smoking have been attributed to an increased incidence of IBD. 20 21 22 23 24…”

Section: Pathogenesis and Clinical Features Of Ibdmentioning

confidence: 99%

“…17 The other key component that plays a role in IBD pathogenesis is the environment. 18,19 Specifically, diet, vitamin D deficiency, exposure to antibiotics, and smoking have been attributed to an increased incidence of IBD. [20][21][22][23][24] Reports suggest that the heritable risk for CD is higher than that for UC, and that there is a higher incidence of IBD in firstdegree relatives of patients with IBD compared with the general population.…”

mentioning

confidence: 99%

The Interface between Inflammatory Bowel Disease, Neuroinflammation, and Neurological Disorders

et al. 2023

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Inflammatory Bowel Disease (IBD) is a complex, chronic inflammatory condition affecting the gastrointestinal tract. IBD has been associated with a variety of neurologic manifestations including peripheral nerve involvement, increased risk of thrombotic, demyelinating and events. Furthermore, an evolving association between IBD and neurodegenerative disorders has been recognized, and early data suggests an increased risk of these disorders in patients diagnosed with IBD. The relationship between intestinal inflammatory disease and neuroinflammation is complex, but the bidirectional interaction between the brain-gut-microbiome axis is likely to play an important role in the pathogenesis of these disorders. Identification of common mechanisms and pathways will be key to developing potential therapies. In this review, we discuss the evolving interface between IBD and neurological conditions, with a focus on clinical, mechanistic, and potentially therapeutic implications.

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“…The gut microbiota, i.e., the complex microbial community living within the intestinal tract in symbiosis with its host, is now recognized as an essential contributor to human health and well-being. High throughput omics data have increasingly revealed mechanisms of interaction between the human host and its commensal microbes ( 1 ). The microbiota degrades food residues and produces many metabolites and compounds that are uptaken by the host, such as short-chain fatty acids (SCFAs), amino acids, and essential vitamins ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Design of a proteolytic module for improved metabolic modeling of Bacteroides caccae

Paulay,

Grimaud,

Caballero

et al. 2024

mSystems

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The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on Bacteroides caccae , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that B. caccae possesses a set of 156 proteases with putative intracellular and extracellular localization and allowed to identify amino acid transporters and metabolic pathways. We developed a fully curated genome-scale metabolic model of B. caccae that incorporated its proteolytic activity and simulated its growth and production of fermentation-related metabolites in response to the different growth media. We validated the model by comparing the predicted phenotype to experimental data. The model accurately predicted B. caccae ’s growth and metabolite production ( R 2 = 0.92 for the training set and R 2 = 0.89 for the validation set). We found that accounting for both ATP consumption related to proteolysis, and whey protein accessibility is necessary for accurate predictions of metabolites production. These results provide insights into B. caccae ’s adaptation to a high-protein diet and its ability to utilize proteins as a source of nutrition. The proposed model provides a useful tool for understanding the feeding mechanism of B. caccae in the gut microbiome. IMPORTANCE Microbial proteolysis is understudied despite the availability of dietary proteins for the gut microbiota. Here, the proteolytic potential of the gut symbiont Bacteroides caccae was analyzed for the first time using pan-genomics. This sketches a well-equipped bacteria for protein breakdown, capable of producing 156 different proteases with a broad spectrum of cleavage targets. This functional potential was confirmed by the enhancement of growth and metabolic activities at high protein levels. Proteolysis was included in a B. caccae metabolic model which was fitted with the experiments and validated on external data. This model pinpoints the links between protein availability and short-chain fatty acids production, and the importance for B. caccae to gain access to glutamate and asparagine to promote growth. This integrated approach can be generalized to other symbionts and upscaled to complex microbiota to get insights into the ecological impact of proteins on the gut microbiota.

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Stool multi-omics for the study of host–microbe interactions in inflammatory bowel disease

Cited by 11 publications

References 125 publications

The Gut Microbiome: A Primer for the Clinician

The Gut Microbiome: A Primer for the Clinician

The Interface between Inflammatory Bowel Disease, Neuroinflammation, and Neurological Disorders

Design of a proteolytic module for improved metabolic modeling of Bacteroides caccae

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