Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice

Rogala, Allison R.; Oka, Akihiko; Sartor, R. Balfour

doi:10.3389/fimmu.2020.00214

Cited by 26 publications

(22 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The changes in adult male mice, where the FMT experiment was carried out, were no longer statistically significant 1 week after reintroduction of the gut microbiota (Manca et al 2020b). Whether or not eCBome signalling alterations in germ-free mice account for some of the metabolic features of these animals, which are characterised, among others, by higher energy expenditure and lower intestinal inflammation and immunity (Wolf 2006, Rogala et al 2020, as well by higher HPA axis activity (Farzi et al 2018), remains to be investigated.…”

Section: :2mentioning

confidence: 99%

The gut microbiome, endocannabinoids and metabolic disorders

Iannotti

Marzo

2021

Journal of Endocrinology

View full text Add to dashboard Cite

Two complex systems are emerging as being deeply involved in the control of energy metabolism. The intestinal microbiota, with its warehouse of genes, proteins and small molecules, i.e. the gut microbiome; and the endocannabinoid system, with its recent extension to a more complex signalling apparatus including more than one hundred lipid mediators and fifty proteins, i.e. the endocannabinoidome. Both systems can become perturbed following bad dietary habits and during obesity, thus contributing to exacerbating this latter condition and its consequences in both peripheral organs and the brain. Here we discuss some of the multifaceted aspects of the regulation and dysregulation of the gut microbiome and endocannabinoidome in energy metabolism and metabolic disorders, with special emphasis on the emerging functional interactions between the two systems. The potential exploitation of this new knowledge for the development of new pharmacological and nutritional approaches against obesity and its consequences is also briefly touched upon.

show abstract

Section: :2mentioning

confidence: 99%

The gut microbiome, endocannabinoids and metabolic disorders

Iannotti

Marzo

2021

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…GUT-103 and GUT-108 were designed based on human data showing that protective functions provided by commensal bacteria are under-represented in the gut microbiome of IBD patients. These functions include the synthesis of SCFAs, indole and its derivatives, bile acid deconjugation and conversion, and competition for the critical nutrient iron and the synthesis of antagonistic molecules to control opportunistic pathogens 3 , 34 . Several animal studies have highlighted the role for SCFAs, especially propionate and butyrate, in regulatory T cell recruitment and function 8 , 12 , 13 , 34 – 36 .…”

Section: Discussionmentioning

confidence: 99%

“…These functions include the synthesis of SCFAs, indole and its derivatives, bile acid deconjugation and conversion, and competition for the critical nutrient iron and the synthesis of antagonistic molecules to control opportunistic pathogens 3 , 34 . Several animal studies have highlighted the role for SCFAs, especially propionate and butyrate, in regulatory T cell recruitment and function 8 , 12 , 13 , 34 – 36 . The recruitment in the colon and extrathymic conditioning of regulatory T cell response by SCFA make these molecules an important link in the crosstalk between the gut microbiome and the immune system.…”

Section: Discussionmentioning

confidence: 99%

Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

Lelie¹,

Oka

Taghavi³

et al. 2021

Nat Commun

Self Cite

105

View full text Add to dashboard Cite

Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.

show abstract

“…Indole can act upon other receptors important to host physiology, including the aryl hydrocarbon receptor AhR. Activation of AhR by indole or other tryptophan metabolites has been shown to protect against colitis in mice (Rogala et al, 2020). There are several microbial-derived tryptophan metabolites that act as AhR agonists and can modulate the gastrointestinal immune cells, enhance barrier function, and inhibit intestinal inflammation (Aoki et al, 2018;Natividad et al, 2018;Roager and Licht, 2018;Rothhammer et al, 2016;Vyhlidalova et al, 2020;Zelante et al, 2013).…”

Section: Examples Of Microbial Metabolite Mimicry In Drug Discoverymentioning

confidence: 99%

Weak Microbial Metabolites: a Treasure Trove for Using Biomimicry to Discover and Optimize Drugs

et al. 2020

Self Cite

View full text Add to dashboard Cite

Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice

Cited by 26 publications

References 106 publications

The gut microbiome, endocannabinoids and metabolic disorders

The gut microbiome, endocannabinoids and metabolic disorders

Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

Weak Microbial Metabolites: a Treasure Trove for Using Biomimicry to Discover and Optimize Drugs

Contact Info

Product

Resources

About