Explore the vast range of titles available.

Gut microbiota produces a wide and diverse array of metabolites that are an integral part of the host metabolome. The emergence of the gut microbiome-brain axis concept has prompted investigations on the role of gut microbiota dysbioses in the pathophysiology of brain diseases. Specifically, the search for microbe-related metabolomic signatures in human patients and animal models of psychiatric disorders has pointed out the importance of the microbial metabolism of aromatic amino acids. Here, we investigated the effect of indole on brain and behavior in rats. Indole is produced by gut microbiota from tryptophan, through the tryptophanase enzyme encoded by the A gene. First, we mimicked an acute and high overproduction of indole by injecting this compound in the cecum of conventional rats. This treatment led to a dramatic decrease of motor activity. The neurodepressant oxidized derivatives of indole, oxindole and isatin, accumulated in the brain. In addition, increase in eye blinking frequency and in c-Fos protein expression in the dorsal vagal complex denoted a vagus nerve activation. Second, we mimicked a chronic and moderate overproduction of indole by colonizing germ-free rats with the indole-producing bacterial species . We compared emotional behaviors of these rats with those of germ-free rats colonized with a genetically-engineered counterpart strain unable to produce indole. Rats overproducing indole displayed higher helplessness in the tail suspension test, and enhanced anxiety-like behavior in the novelty, elevated plus maze and open-field tests. Vagus nerve activation was suggested by an increase in eye blinking frequency. However, unlike the conventional rats dosed with a high amount of indole, the motor activity was not altered and neither oxindole nor isatin could be detected in the brain. Further studies are required for a comprehensive understanding of the mechanisms supporting indole effects on emotional behaviors. As our findings suggest that people whose gut microbiota is highly prone to produce indole could be more likely to develop anxiety and mood disorders, we addressed the issue of the inter-individual variability of indole producing potential in humans. An investigation of metagenomic data focused on the A gene products definitively proved this inter-individual variability.

The gut microbiota has been increasingly linked to metabolic health and disease over the last few decades. Several factors have been suggested to be involved in lipid metabolism and metabolic responses. One mediator that has gained great interest as a clinically important enzyme is bile salt hydrolase (BSH). BSH enzymes are widely distributed in human gastrointestinal microbial communities and are believed to play key roles in both microbial and host physiology. In this review, we discuss the current evidence related to the role of BSHs in health and provide useful insights that may pave the way for new therapeutic targets in human diseases.

Serine proteases are extensively known to play key roles in many physiological processes. However, their dysregulation is often associated to several diseases including inflammatory bowel diseases (IBD). Here, we used specific substrates to monitor fecal protease activities in a large cohort of healthy and IBD patients. Of interest, serine protease activity was 10-fold higher in IBD fecal samples compared to healthy controls. Moreover, functional analysis of these fecal proteolytic activities revealed that the most increased activities are trypsin-like, elastase-like and cathepsin G-like. We also show for the first time, an increase of proteinase 3-like activity in these samples compared to controls. Results presented here will guide further investigations to better understand the relevance of these peptidases in IBD.

Abstract Serine proteases are involved in many biological processes and are associated with irritable bowel syndrome (IBS) pathology. An increase in serine protease activity has been widely reported in IBS patients. While most of the studies focused on host proteases, the contribution of microbial proteases are poorly studied. In the present study, we report the analysis of proteolytic activities in fecal samples from the first Tunisian cohort of IBS-M patients and healthy individuals. We demonstrated, for the first time, that metalloproteases activities were fourfold higher in fecal samples of IBS patients compared to controls. Of interest, the functional characterization of serine protease activities revealed a 50-fold increase in trypsin-like activities and a threefold in both elastase- and cathepsin G-like activities. Remarkably, we also showed a fourfold increase in proteinase 3-like activity in the case of IBS. This study also provides insight into the alteration of gut microbiota and its potential role in proteolytic modulation in IBS. Our results stressed the impact of the disequilibrium of serine proteases, metalloproteases and gut microbiota in IBS and the need of the further characterization of these targets to set out new therapeutic approaches.

Canine inflammatory bowel diseases (IBD) are of increasing interest in veterinary medicine. They refer to complex and debilitating conditions of dogs’ gastrointestinal tract. Although little evidence for causal inferences is currently available, it is believed that IBD pathophysiology entails intricate interactions between environmental factors, the intestinal immune system, and the microbial communities that colonize the gut. To better understand the mechanisms underlying these disorders, leveraging factors associated with the development of these diseases is imperative. Of these factors, emerging evidence supports the role of dietary patterns as key players influencing the composition and function of gut microbes, with subsequent effects on health and disease. In this review, we particularly focus on addressing IBD in dogs and discuss how specific nutrients may elicit or relieve gut inflammation. Gaining mechanistic insights into such interplay and the underpinning mechanisms is key to inferring dietary recommendations, and setting up new and promising therapeutics.

In recent years, microbiomes and their potential applications for human, animal or plant health, food production and environmental management came into the spotlight of major national and international policies and strategies. This has been accompanied by substantial R&D investments in both public and private sectors, with an increasing number of products entering the market. Despite widespread agreement on the potential of microbiomes and their uses across disciplines, stakeholders and countries, there is no consensus on what defines a microbiome application. This often results in non‐comprehensive communication or insufficient documentation making commercialisation and acceptance of the novel products challenging. To showcase the complexity of this issue we discuss two selected, well‐established applications and propose criteria defining a microbiome application and their conditions of use for clear communication, facilitating suitable regulatory frameworks and building trust among stakeholders. Advances in microbiome research have resulted in microbiome applications increasingly entering the market. Commercialisation of these novel applications is associated with challenges, often caused by non‐comprehensive communication or insufficient documentation. Criteria defining a microbiome application and their conditions of use for clear communication, facilitating suitable regulatory frameworks and building trust among stakeholders are presented.

Accumulating data show the involvement of intestinal microbiota in the development and maintenance of numerous diseases. Many environmental factors influence the composition and function of the gut microbiota. An animal model subjected to the same environmental constraints that will allow better characterization of the microbiota–host dialogue is awaited. The domestic dog has physiological, dietary and pathological characteristics similar to those of humans and shares the domestic environment and lifestyle of its owner. This review exposes how the domestication of dogs has brought them closer to humans based on their intrinsic and extrinsic similarities which were discerned through examining and comparing the current knowledge and data on the intestinal microbiota of humans and canines in the context of several spontaneous pathologies, including inflammatory bowel disease, obesity and diabetes mellitus.

Inflammatory bowel diseases (IBDs) have emerged as a public health problem worldwide with a limited number of efficient therapeutic options despite advances in medical therapy. Although changes in the gut microbiota composition are recognized as key drivers of dysregulated intestinal immunity, alterations in bile acids (BAs) have been shown to influence gut homeostasis and contribute to the pathogenesis of the disease. In this review, we explore the interactions involving BAs and gut microbiota in IBDs, and discuss how the gut microbiota–BA–host axis may influence digestive inflammation.

The overarching biological impact of microbiomes on their hosts, and more generally their environment, reflects the co-evolution of a mutualistic symbiosis, generating fitness for both. Knowledge of microbiomes, their systemic role, interactions, and impact grows exponentially. When a research field of importance for planetary health evolves so rapidly, it is essential to consider it from an ethical holistic perspective. However, to date, the topic of microbiome ethics has received relatively little attention considering its importance. Here, ethical analysis of microbiome research, innovation, use, and potential impact is structured around the four cornerstone principles of ethics: Do Good; Don’t Harm; Respect; Act Justly. This simple, but not simplistic approach allows ethical issues to be communicative and operational. The essence of the paper is captured in a set of eleven microbiome ethics recommendations, e.g., proposing gut microbiome status as common global heritage, similar to the internationally agreed status of major food crops.

Much evidence indicates that metabolic syndrome is strongly correlated with a decrease in nitric oxide and an increase in oxidative stress leading to cardiovascular alterations. In recent years, gut microbiota has emerged as a new contributor to the metabolic syndrome establishment and associated cardiovascular diseases, but the underlying mechanisms remain unclear. We hypothesized that a positive modulation of cyclic guanosine monophosphate (cGMP) pathway, through phosphodiesterase type 5 (PDE5) inhibition could prevent cardiovascular alterations and gut dysbiosis that may be associated to metabolic syndrome. Spontaneously hypertensive rats (SHR) were randomly divided into 4 groups: control, cafeteria diet (CD) and sildenafil citrate treated groups (5mg/kg per os) were given either a CD or a standard chow diet for 10 weeks. Body weight, arterial blood pressure and glucose tolerance test were monitored. At the 10th week, cardiac inotropy and coronary perfusion pressure were evaluated on isolated heart according to Langendorff method. Cumulative concentration response curves to phenylephrine and acetylcholine were determined on thoracic aorta rings for vascular reactivity evaluation. Faecal samples were collected for the gut microbiota analysis. Compared to the control group, CD-fed rats showed a significant increase in body weight gain, arterial blood pressure and were glucose intolerant. This group showed also a decrease in β-adrenoceptor-induced cardiac inotropy and coronary vasodilation. Gut microbiota analysis revealed a significant reduction in the abundance of Lactobocillus spp in cafeteria diet-fed rats when compared to the control ones. Sildenafil citrate long-term treatment decreased weight gain and arterial blood pressure, improved coronary vasodilation and reduced α1-adrenoceptor-induced vasoconstriction in CD group. However, it did not reverse gut dysbiosis induced by chronic CD feeding. These results suggest that cGMP pathway targeting may be a potential therapeutic strategy for the management of the metabolic syndrome and associated cardiovascular disorders.