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Bacterial bile salt hydrolase activity: from selection to impact on host metabolism and microbiota
University College Cork
Bile acids (BAs), biological detergents for nutrient digestion, are recognized as local and systemic signaling molecules which interact with a variety of receptors central to host metabolism. While BAs are synthesized in the liver, the range and diversity of bile acids available to interact with these receptors is dictated by the gut microbiota. Amongst gut represented microbial phyla the function of bile salt hydrolase (BSH) activity is highly conserved. In many disease states where microbial populations are affected BA metabolism is similarly altered. The interplay between bile acid, microbial adjustment, diet and nutrient digestion is highly complex and has clear roles in health and disease. For all of these reasons this co-evolved and maintained function of the gut microbiota is therefore a plausible target for therapeutic applications. The diversity of activity among bile altering bile salt hydrolase (BSH) enzymes is being recognized. This study highlights this diversity in functionally isolating and characterizing specific classes of BSH. Here, new BSH active isolates of porcine and human origin were isolated through rational and non-rational selection methods. The specific activity of each strain was described and they were evaluated for potential probiotic use relative to EFSA guidelines. All isolates were identified taxonomically through a combination of approaches including RAPD, rDNA and MLST. From rational based screening a single isolate carrying 3 putative BSH alleles now designated Lactobacillus salivarius APC1486 was identified as a new strain. Two of these BSHs are predicted as active on the basis of in silico analysis. The influence of this isolate was analysed, in pre-clinical studies, to determine its effects on the microbiota, metabolites and host metabolism under different dietary conditions to reveal that mode of delivery, dose and diet altered colonization efficiency and induced differential effects on host metabolism and physiology. Not all of these effects could be attributed to BSH activity. These in vivo studies also highlight the importance of these factors for probiotic efficacy. Formula fed infant BSH active Enterococcus avium strains were isolated on the basis of functional screening. They were also identified to species level and characterized according to EFSA guidelines and functional BSH activity. This particular species is not well characterized in the literature and this is the first report of their functionality in the infant gut. In contrast, inhibiting this BSH enzyme activity has been proposed within the agricultural industry in a bid to reduce the usage of antibiotic growth promoters in poultry. In collaboration with Prof. Jun Lin’s group (The University of Tennessee Institute of Agriculture) we will also focus on the use of three compounds: caffeic acid phenethyl ester, riboflavin and carnosic acid which have recently been identified as BSH inhibiting compounds. If these compounds are applied in vivo can they reduced BSH activity and is this reduction of BSH activity beneficial in improving growth efficiency in broiler chickens. To analyse this bile acid extraction and quantification was performed on ileal contents and plasma from 28 day old chickens following 21 days of treatment. Taken together, this thesis will highlight the importance that BSH activity can confer to a bacterial strain and how this enzymes activity may be manipulated to confer differential health benefits depending on the host and its specific needs.
Bile , Bile metabolism , Lactobacillus , Probiotics
Long, S-L. 2019. Bacterial bile salt hydrolase activity: from selection to impact on host metabolism and microbiota. PhD Thesis, University College Cork.