Humans as holobionts: implications for prevention and therapy

Guchte, Maarten van de; Blottière, Hervé M.; Doré, Joël

doi:10.1186/s40168-018-0466-8

Cited by 124 publications

(94 citation statements)

References 41 publications

(45 reference statements)

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Section: Microbiomics In Ibd: From Postulated Theories To Known Diffementioning

confidence: 99%

“…In the healthy state, the gut homeostasis is maintained [50]. The intestinal immune responses are regulated in order to provide a protective immunity against potential invading pathogens, while limiting any immune reaction in response to innocuous microbes and dietary antigens [50,51]. Changes in the gut microbial compositions or microbial dysbiosis, is defined as a decrease in the intestinal microbial diversity resulting in an imbalance between commensal "protective" versus potential pathogens "harmful", thus promoting an excessive intestinal inflammation [52].…”

Section: Microbiomics In Ibd: From Postulated Theories To Known Diffementioning

confidence: 99%

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Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

2019

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Background: Inflammatory Bowel Disease (IBD) is a multifactorial chronic disease. Understanding only one aspect of IBD pathogenesis does not reflect the complex nature of IBD nor will it improve its clinical management. Therefore, it is vital to dissect the interactions between the different players in IBD pathogenesis in order to understand the biology of the disease and enhance its clinical outcomes. Aims:To provide an overview of the available omics data used to assess the potential mechanisms through which various players are contributing to IBD pathogenesis and propose a precision medicine model to fill the current knowledge gap in IBD.Results: Several studies have reported microbial dysbiosis, immune and metabolic dysregulation in IBD patients, however, this data is not sufficient to create signatures that can differentiate between the disease subtypes or between disease relapse and remission. Conclusions:We summarized the current knowledge in the application of omics in IBD patients, and we showed that the current knowledge gap in IBD hinders the improvements of clinical decision for treatment as well as the prediction of disease relapse. We propose one way to fill this gap by implementing integrative analysis of various omics datasets generated from one patient at a single time point.

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Section: Microbiomics In Ibd: From Postulated Theories To Known Diffementioning

confidence: 99%

Section: Microbiomics In Ibd: From Postulated Theories To Known Diffementioning

confidence: 99%

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

2019

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“…An adverse change induces a gut dysbiosis which disrupts the symbiosis maintained by the MGB axis. Indeed, a gut dysbiosis has been linked to various health conditions, such as obesity, IBS, schizophrenia, Parkinson's disease and MDD (Sherwin et al, 2016;Thursby and Juge, 2017;van de Guchte et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

et al. 2020

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The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.

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“…In the case of uncultured species, it is impossible to inactivate or delete genes. Notably, these species make up more than 70% of the human gut ecosystem (40). In addition, transmembrane proteins cannot be studied as easily as soluble proteins.…”

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confidence: 99%

Harvesting of Prebiotic Fructooligosaccharides by Nonbeneficial Human Gut Bacteria

Wang

Tauzin

Laville

et al. 2020

mSphere

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Prebiotic oligosaccharides, such as fructooligosaccharides, are increasingly being used to modulate the composition and activity of the gut microbiota. However, carbohydrate utilization analyses and metagenomic studies recently revealed the ability of deleterious and uncultured human gut bacterial species to metabolize these functional foods. Moreover, because of the difficulties of functionally profiling transmembrane proteins, only a few prebiotic transporters have been biochemically characterized to date, while carbohydrate binding and transport are the first and thus crucial steps in their metabolization. Here, we describe the molecular mechanism of a phosphotransferase system, highlighted as a dietary and pathology biomarker in the human gut microbiome. This transporter is encoded by a metagenomic locus that is highly conserved in several human gut Firmicutes, including Dorea species. We developed a generic strategy to deeply analyze, in vitro and in cellulo, the specificity and functionality of recombinant transporters in Escherichia coli, combining carbohydrate utilization locus and host genome engineering and quantification of the binding, transport, and growth rates with analysis of phosphorylated carbohydrates by mass spectrometry. We demonstrated that the Dorea fructooligosaccharide transporter is specific for kestose, whether for binding, transport, or phosphorylation. This constitutes the biochemical proof of effective phosphorylation of glycosides with a degree of polymerization of more than 2, extending the known functional diversity of phosphotransferase systems. Based on these new findings, we revisited the classification of these carbohydrate transporters.IMPORTANCE Prebiotics are increasingly used as food supplements, especially in infant formulas, to modify the functioning and composition of the microbiota. However, little is currently known about the mechanisms of prebiotic recognition and transport by gut bacteria, while these steps are crucial in their metabolism. In this study, we established a new strategy to profile the specificity of oligosaccharide transporters, combining microbiomics, genetic locus and strain engineering, and state-of-the art metabolomics. We revisited the transporter classification database and proposed a new way to classify these membrane proteins based on their structural and mechanistic similarities. Based on these developments, we identified and characterized, at the molecular level, a fructooligosaccharide transporting phosphotransferase system, which constitutes a biomarker of diet and gut pathology. The deciphering of this prebiotic metabolization mechanism by a nonbeneficial bacterium highlights the controversial use of prebiotics, especially in the context of chronic gut diseases.

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Humans as holobionts: implications for prevention and therapy

Cited by 124 publications

References 41 publications

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

Harvesting of Prebiotic Fructooligosaccharides by Nonbeneficial Human Gut Bacteria

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