Team Bruno POT

Lactic Acid Bacteria and Mucosal Immunity

The LABMI team is currently a team of the Centre of Infection and Immunity Lille and has a major interest in health applications of lactic acid bacteria (LAB). In an attempt to substantiate the effectiveness of the so-called ‘probiotic’ LAB, we have developed and used different standardized in vitro and in vivo models.

While screening immune-modulation properties we observed strong strain-specific differences, yielding strains with highly different properties that was used as the basic material for a number of comparative research projects aiming at understanding the underlying mechanisms of action. Knowledge about mechanisms is of interest to the industry and the medical community, as it facilitates the definition of suitable biomarkers and will guide the selection process for strains for improved, dedicated health applications. A second research axis of the laboratory focuses on the demonstration that recombinant LAB can efficiently deliver vaccine antigens and therapeutic molecules. The direct delivery of vaccines or therapeutic molecules at the host’s mucosal surfaces by safe LAB with inherent adjuvant properties has led to promising perspectives for their development as prophylactic or therapeutic tools. The lab has also shown that the activities of selected LAB can be enhanced by genetic modification, for example by changing selected target structures at the bacterial surface.

 

The intestine is a complex and dynamic ecosystem containing about one thousand bacterial species, comprising potential pathogens, commensal bacteria or microorganisms beneficial for the health of the host. This microbiota establishes shortly after birth and is essential in priming the immune system, in contributing to gut homeostasis and in intestinal functionality. The emergence of a number of immunological disorders, such as Th2-driven allergic diseases or disorders driven by Th1 effector cells, like inflammatory bowel diseases (IBD), type 1 diabetes and multiple sclerosis, have been attributed to a modern lifestyle linked to certain dietary, hygienic and medical habits. Notably, IBD was suggested to be associated with abnormal immune responses and a breakdown of tolerance against the indigenous microflora. It has been shown recently that recognition of commensal bacteria by Toll like receptors (TLR) at the host cell surface plays a crucial role in the maintenance of intestinal homeostasis. Largely used in a variety of food fermentation processes, certain lactic acid bacteria (LAB) are well known to have health benefits in humans or animals. The proposal of probiotics in a medical context has recently gained a lot of momentum, and therapeutic / prophylactic capacities have been demonstrated both in animal models and in clinical studies. Despite some successes, a number of studies did not yield significant results. The failure of these studies in many cases can be linked to the lack of a proper strain selection prior to the trial and to the definition of endpoints, which are defined according to criteria that apply to clinical trials with pharmaceutical endpoints. The use of probiotics as an add-on therapy in immune disorder treatments will in many cases prove to be very rewarding, given that adapted strains and proper administration / delivery protocols are used.

In this respect we are currently expanding our research field to study in depth the mechanisms underlying the observed beneficial effects and in particular on the role of the peptidoglycan andNOD2 signalling in the anti-inflammatory capacities of lactobacilli. This could lead to the development of potent anti-inflammatory preparations that can be used in a prophylactic approach to fight IBD. In the meantime we hope to obtain positive results from the ongoing clinical trial in Belgium, where a Bifidobacterium breve strain is used to extend remission time in patients with ulcerative colitis and pouchitis.

More recently we started to explore to which extend the anti-inflammatory activity of probiotic strains might be useful in the therapy of obesity (collaboration with Isabelle Wolowczuk, CNRS) and in reducing the development of glucose tolerance.

 

In an attempt to better understand the observed efficiency of selected probiotics to treat active phases of Clostridium difficile diarrhea, we are currently optimizing an infection model that will allow us to compare different strains and to study the underlying mechanisms of the well-documented protection against this pathogen.

We furthermore extend the possible application fields of LAB in the framework of a national ANR research project (ANR 09-CESA-016) that will study the potential of probiotic bacteria and yeast, to reduce the toxicity of heavy metals like cadmium and lead, taken up from the environment or through the diet.

Finally, since 2010 we are also optimizing the luciferase labeling of LAB, allowing detection and follow-up live microorganisms along the digestive tract of small animals. This project will allow us to gain better insight in the physical aspects of host – bacteria interaction and may be an interesting tool to follow the faith of different LAB strains after ingestion.

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