No abstract

For thousands of years, lactic acid bacteria (LAB) have been interwoven with our food supply. The earliest evidence of milk use dates back to 7,000 years BCE (1), while cheeses were produced as early as 6,000 years BCE (2). Advances in our understanding of the microbial world in the past couple of centuries have enabled microbiology-based food manufacturing on an industrial scale. Not only are LAB used to ferment dairy products, but they are also applied to pickle vegetables, to cure meats, and to produce alcoholic beverages such as wine and sake (3, 4). This long history of safe consumption led to the consideration that many LAB strains are Generally Recognized As Safe (GRAS). As early as 1906, LAB were linked to the promotion of human health. The Russian Nobel laureate Élie Metchnikoff hypothesized that ingestion of yogurt prolonged life in Eastern European populations by reducing "putrefying" [sic] bacteria. His linkage of the perceived longevity of the Eastern European populations with consumption of fermented dairy products (5) made him the grandfather of modern probiotics. Probiotics are defined as "live microorganisms, which when administrated in adequate amounts, confer a health benefit to the host" (6). Metchnikoff's probiotic theory of life prolongation was never directly tested, and researchers reported in 1924 that LAB present in yogurt, specifically Lactobacillus bulgaricus, most likely do not reduce "putrifying" bacteria in the intestine because L. bulgaricus did not survive gastrointestinal (GI) transit (7). Other groups challenged this finding. Elli et al. demonstrated that both Streptococcus thermophilus and L. bulgaricus were present in human feces after yogurt ingestion (8). Regardless, Metchnikoff's theory was born that bacteria could be health-promoting through modifying the composition of the bacterial population that inhabits our intestine. In 2017, this translates into the use of (tailored) probiotics to modify the gut microbiota to promote human health. Today we can engineer LAB in general, and recent advances have made it possible to engineer select probiotic strains in a high-throughput manner. Also, we have an increased appreciation and understanding of the role of the gut microbiota in health and disease. Thus, the contemporary application of tailored probiotics to promote human health Bugs as Drugs: Therapeutic Microbes for the Prevention and Treatment of Disease

No abstract

Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence intestinal diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate preferences and impact on C. difficile remain elusive. Here, we survey the diversity of Lactobacillus BSHs and unravel the structural basis of their substrate preference. We show that leveraging BSH activity and specificity is an effective strategy to prevent C. difficile growth in clinically relevant CDI models. A range of non-canonical conjugated BAs is also identified, comprising unique BSH substrates that also inhibit C. difficile spore germination. These findings establish BSHs as intestinal enzymes essential to BA homeostasis and colonization resistance against C. difficile.

No abstract