Gut microbiota: next frontier in understanding human health and development of biotherapeutics

Satya Prakash, Laetitia Rodes, Michael Coussa-Charley, Catherine Tomaro-DuchesneauBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec, CanadaAbstract: The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.Keywords: gut microbiota, human health, dysbiosis, biotherapeutics, probiotics, microencapsulatio

Use of Artificial Cell Microcapsule Containing Thalidomide for Treating TNBS-induced Crohn's Disease in Mice

In this study, we examined the in-vivo characteristics of a novel microencapsulated thalidomide formulation in a murine model of experimental Crohn's disease. Crohn's disease was induced with a single intra-colonic injection of 120 mg/kg of bodyweight of 2,5,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 30% ethanol in Balb/c mice. Level of tumor necrosis factor alpha (TNF-), interleukin one beta (IL-1), interleukin 6 (IL-6) and nitric oxide (NO) were measured in tissue homogenate. Moreover, myeloperoxidase (MPO) activity was determined to assess the extent of neutrophil infiltration. Dose response study showed that treating the mice with microencapsulated thalidomide (100 mg/kg of bodyweight) for two weeks significantly decreased the degree of intestinal inflammation related to Crohn’s disease. Higher and lower doses (0, 25, 50 and 200 mg/kg of bodyweight) did not exhibit comparable effects. The present study validates the success of alginate-poly-L-lysine-alginate (APA) microcapsules containing thalidomide in reducing colonic inflammation, and proposes a potential remedy for Crohn’s disease

Transit Time Affects the Community Stability of Lactobacillus and Bifidobacterium Species in an In Vitro Model of Human Colonic Microbiotia

Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy

Lactobacillus fermentum NCIMB 5221 has a greater ferulic acid production compared to other ferulic acid esterase producing Lactobacilli

Ferulic acid (FA) is an antioxidant compound known to neutralize free radicals, such as reactive oxygen species (ROS). These free radicals have been shown to be involved in DNA damage, cancer and aging. The administration of FA, as an oral therapeutic is hampered by its absorption in the small intestine followed by its quick excretion. Colonic microbial enzymes have been shown to produce FA. In this article, selected Lactobacillus strains were screened for FA production by Ferulic Acid Esterase (FAE), as determined by the release of free FA from a natural substrate, ethyl ferulate (EFA). Using a MRS-EFA plate clearing assay, L. fermentum ATCC 11976, L. reuteri ATCC 23272 and L. fermentum NCIMB 5221 all showed clearance zones of 10mm in diameter, confirming FAE activity. Results show that L. fermentum NCIMB 5221 is the most efficient FA producing strain, producing 0.168±0.001mg/mL FA following 48 hours of incubation in 0.296mg/mL EFA. We also investigated the total antioxidant capacity of L. fermentum NCIMB 5221 when grown in culture. Results suggest that, due to its FA production, L. fermentum NCIMB 5221 has potential for use as a future therapeutic