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Delivery of Metabolically Neuroactive Probiotics to the Human Gut.

ABSTRACT: The human microbiome is a rich factory for metabolite production and emerging data has led to the concept that orally administered microbial strains can synthesize metabolites with neuroactive potential. Recent research from ex vivo and murine models suggests translational potential for microbes to regulate anxiety and depression through the gut-brain axis. However, so far, less emphasis has been placed on the selection of specific microbial strains known to produce the required key metabolites and the formulation in which microbial compositions are delivered to the gut. Here, we describe a double-capsule technology to deliver high numbers of metabolically active cells derived from the 24-strain probiotic product SH-DS01 to the gastrointestinal tract, including the small intestine, where immune responses and adsorption of metabolites into the bloodstream occur. Based on its genome sequence, Limosilactobacillus reuteri SD-LRE2-IT was predicted to have the genetic capacity to de novo produce a specific metabolite of interest to brain health, vitamin B12, which could be confirmed in vitro. Taken together, our data conceptualizes the importance of rationally defined microbial strain characterization based on genomics and metabolomics data, combined with carefully designed capsule technology for delivery of live cells and concomitant functionality in and beyond the gut ecosystem.

SUBMITTER: Bron PA

PROVIDER: S-EPMC8431588 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Four delivery routes, via, feed, water, litter and oral gavage, were examined for their efficacy in delivering a novel probiotic of poultry origin, Lactobacillus johnsonii, to broilers. Seven treatments of 6 replicates each were allocated using 336 one-day-old Cobb broiler chicks. The treatments consisted of a basal diet with the probiotic candidate, L. johnsonii, added to the feed, and three treatments with L. johnsonii added to the drinking water, sprayed on the litter, or gavaged orally. In addition, a positive control treatment received the basal diet supplemented with zinc-bacitracin (ZnB, 50 mg/kg). The probiotic strain of L. johnsonii was detected in the ileum of the chicks for all four delivery routes. However, the addition of L. johnsonii as a probiotic candidate did not improve body weight gain, feed intake and feed conversion ratio of broiler chickens raised on litter during the 5-week experimental period regardless of the route of administration. The probiotic treatments, regardless of the routes of delivery, affected (P < 0.05) the pH of the caecal digesta and tended (P = 0.06) to affect the pH of the ileal digesta on d 7, but the effect disappeared as the birds grew older. All probiotic treatments reduced the number of Enterobacteria in the caeca on d 21, and tended (P < 0.054) to reduce it in the ileum and caeca on d 7 and in the ileum on d 21 compared with the controls. The probiotic also tended to increase the number of lactic acid bacteria and lactobacilli in the ileum and caeca on d 7, but this trend was not evident on d 21. The trend appeared most pronounced when the probiotic was delivered orally or via litter. The probiotic also decreased (P < 0.05) the population of Clostridium perfringens rapidly from an early age to d 21 in the caeca, leading to a 3-fold decrease in the number of C. perfringens between d 7 and 21. It also showed that the probiotic treatment presented the lowest number of C. perfringens in the caeca. Delivery of the probiotic through feed, water and litter increased (P < 0.01) the weight of the pancreas on d 21, but the probiotic did not affect other morphometric parameters of the gut. Furthermore, the probiotic did not affect the pH and the concentrations of short chain fatty acids and lactic acid in either the ileum or caeca.

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Delivery of Metabolically Neuroactive Probiotics to the Human Gut.

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