RESUMO
Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.
Assuntos
Comportamento Animal/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Penicilinas/administração & dosagem , Penicilinas/farmacologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Caracteres Sexuais , Comportamento Social , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Masculino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/microbiologiaRESUMO
Current prebiotics are predominantly carbohydrates. However, great competition exists among gut microbes for the scarce protein in the colon, as most consumed protein is digested and absorbed in the small intestine. Herein we evaluated in-vivo novel next-generation prebiotics: protein-containing-prebiotics, for selectively-targeted delivery of protein to colonic probiotics, to boost their growth. This system is based on micellar-particles, composed of Maillard-glycoconjugates of 2'-Fucosyllactose (2'-FL, human-milk-oligosaccharide) shell, engulfing lactoferrin peptic-then-tryptic hydrolysate (LFH) core. This core-shell structure lowers protein-core digestibility, while the prebiotic glycans are hypothesized to serve as molecular-recognition ligands for selectively targeting probiotics. To study the efficacy of this novel prebiotic, we fed C57BL/6JRccHsd mice with either 2'-FL-LFH Maillard-glycoconjugates, unconjugated components (control), or saline (blank). Administration of 2'-FL-LFH significantly increased the levels of short-chain-fatty-acids (SCFAs)-producing bacterial families (Ruminococcaceae, Lachnospiraceae) and genus (Odoribacter) and the production of the health-related metabolites, SCFAs, compared to the unconjugated components and to saline. The SCFAs-producing genus Prevotella significantly increased upon 2'-FL-LFH consumption, compared to only moderate increase in the unconjugated components. Interestingly, the plasma-levels of inflammation-inducing lipopolysaccharides (LPS), which indicate increased gut-permeability, were significantly lower in the 2'-FL-LFH group compared to the unconjugated-components and the saline groups. We found that Maillard-glycoconjugates of 2'-FL-LFH can serve as novel protein-containing prebiotics, beneficially modulating gut microbial composition and its metabolic activity, thereby contributing to host health more effectively than the conventional carbohydrate-only prebiotics.
Assuntos
Microbioma Gastrointestinal , Prebióticos , Trissacarídeos , Animais , Camundongos , Promoção da Saúde , Lactoferrina , Camundongos Endogâmicos C57BLRESUMO
The early detection of spoilage microorganisms and food pathogens is of paramount importance in food production systems. We propose a novel strategy for the early detection of food production defects, harnessing the product microbiome. We hypothesize that by establishing microbiome datasets of proper and defective batches, indicator bacteria signaling production errors can be identified and targeted for rapid quantification as part of routine practice. Using the production process of pastrami as a model, we characterized its live microbiome profiles throughout the production stages and in the final product, using propidium monoazide treatment followed by 16S rDNA sequencing. Pastrami demonstrated product-specific and consistent microbiome profiles predominated by Serratia and Vibrionimonas, with distinct microbial signatures across the production stages. Based on the established microbiome dataset, we were able to detect shifts in the microbiome profile of a defective batch produced under lactate deficiency. The most substantial changes were observed as increased relative abundances of Vibrio and Lactobacillus, which were subsequently defined as potential lactate-deficiency indicators. PMA-qPCR efficiently detected increased levels of these species, thus proving useful in rapidly pinpointing the production defect. This approach offers the possibility of the in-house detection of defective production events with same-day results, promoting safer food production systems.
RESUMO
Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.