A Modern-World View of Host-Microbiota-Pathogen Interactions.

The microbiota-the diverse set of commensal microbes that normally colonize humans-represents the first line of defense against infectious diseases. In this review, we summarize the direct and indirect mechanisms by which the microbiota modulates susceptibility to, and severity of, infections, with a focus on immunological mechanisms. Moreover, we highlight some of the ways that modern-world lifestyles have influenced the structure-function relationship between the microbiota and infectious diseases. Ultimately, understanding how the microbiota influences infectious risks will facilitate development of microbiota-derived therapeutics that bolster host defenses.

Efficacy of probiotic treatment as post-exposure prophylaxis for COVID-19: A double-blind, Placebo-Controlled Randomized trial.

BACKGROUND & AIMS: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 continue to be needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; thus, probiotics may be a low-risk, low-cost, and easily implementable modality to reduce risk of COVID-19. METHODS: In this initial study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lacticaseibacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes. RESULTS: Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4 % vs. 42.9 %, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8 % vs. 15.4 %, p = 0.17). CONCLUSIONS: This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤7 days post-COVID-19 exposure, but not overall incidence. This initial work may inform future COVID-19 prevention studies worldwide, particularly in developing nations where Lacticaseibacillus probiotics have previously been utilized to reduce other non-COVID infectious-morbidity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04399252, Date: 22/05/2020. https://clinicaltrials.gov/ct2/show/NCT04399252.

Ruminococcus gnavus and Limosilactobacillus reuteri Regulate Reg3γ Expression through Multiple Pathways.

Epithelium-derived antimicrobial peptides represent an evolutionarily ancient defense mechanism against pathogens. Regenerating islet-derived protein 3 γ (Reg3γ), the archetypal intestinal antimicrobial peptide, is critical for maintaining host-microbe interactions. Expression of Reg3γ is known to be regulated by the microbiota through two different pathways, although it remains unknown whether specific Reg3γ-inducing bacteria act via one or both of these pathways. In recent work, we identified Ruminococcus gnavus and Limosilactobacillus reuteri as commensal bacteria able to induce Reg3g expression. In this study, we show these bacteria require myeloid differentiation primary response protein 88 and group 3 innate lymphoid cells for induction of Reg3γ in mice. Interestingly, we find that R. gnavus and L. reuteri suppress Reg3γ in the absence of either myeloid differentiation primary response protein 88 or group 3 innate lymphoid cells. In addition, we demonstrate that colonization by these bacteria is not required for induction of Reg3γ, which occurs several days after transient exposure to the organisms. Taken together, our findings highlight the complex mechanisms underlying microbial regulation of Reg3γ.