Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory ...bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection.
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•Influenza alters the production of SCFAs by the gut microbiota•The dysbiotic microbiota transfers susceptibility to respiratory bacterial infection•Supplementation with acetate restores the killing activity of alveolar macrophages•Activation of the SCFA receptor FFAR2 protects against bacterial superinfection
Sencio et al. provide insights into the mechanisms that underlie bacterial superinfection post-influenza. The authors demonstrate that influenza infection remotely alters the production of short-chain fatty acids (SCFAs) by the gut microbiota. Supplementation with acetate or pharmacological activation of the SCFA receptor FFAR2 reduces susceptibility to secondary bacterial infection.
Along with respiratory tract disease
, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an ...experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection. As a likely result of bacterial component translocation, gene expression of inflammatory markers was upregulated in the liver. These changes occurred concomitantly with an alteration of the composition of the gut microbiota and with a decreased production of the fermentative, gut microbiota-derived products short-chain fatty acids (SCFAs). Gut inflammation and barrier dysfunction during influenza were not attributed to reduced food consumption, which caused in part gut dysbiosis. Treatment of IAV-infected mice with SCFAs was associated with an enhancement of intestinal barrier properties, as assessed by a reduction in the translocation of dextran and a decrease in inflammatory gene expression in the liver. Lastly, SCFA supplementation during influenza tended to reduce the translocation of the enteric pathogen Salmonella enterica serovar Typhimurium and to enhance the survival of doubly infected animals. Collectively, influenza virus infection can remotely impair the gut's barrier properties and trigger secondary enteric infections. The latter phenomenon can be partially countered by SCFA supplementation.
Purpose of Review
Probiotics intake may be considered beneficial by prospective and pregnant mothers, but their effects on offspring development are incompletely understood. The purpose of this ...review was to examine recent pre-clinical and clinical studies to understand how maternal probiotics exposure affects offspring health outcomes.
Recent Findings
Effects were investigated in the context of supporting offspring growth, intestinal health, and gut microbiota, preventing allergic diseases, supporting neurodevelopment, and preventing metabolic disorders in pre-clinical and clinical studies. Most human studies focused on infancy outcomes, whereas pre-clinical studies also examined outcomes at adolescence and young adulthood. While still understudied, both pre-clinical and clinical studies propose epigenetic modifications as an underlying mechanism. Optimal timing of intervention remains unclear.
Summary
Administration of selected probiotics to mothers has programming potential for sustaining life-long health of offspring. Administration protocols, specific windows of susceptibility, and individual-specific responses need to be further studied.
Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or ...freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.
Fecal microbiota transplantation is now recommended for treating recurrent forms ofClostridioides difficileinfection. Recent studies have reported protocols using capsules of either frozen or ...freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficileproperties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance ofClostridioides difficileinfection in a preclinical murine model with a survival rate of 70%versus53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment ofClostridioides difficileinfection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.
Probiotics intake may be considered beneficial by prospective and pregnant mothers but their effects on offspring development are underexplored. The maternal gut microbiota is a determinant of early ...offspring gut microbial colonization patterns and pre-conception may be a critical period. Our aim was to assess the programming effects of a probiotic Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 mixture, which is known to support intestinal homeostasis in infancy, on the temporal dynamics of offspring gut microbiota functions.
Female C57BL/6 specific pathogen free mice received sterile or probiotic-supplemented water starting one week before mating and until weaning (postnatal day, PND, 21). Offspring remained on their respective mother’s treatment from PND 21 to 36. Offspring cecal microbiota was profiled at PND 14, 21, and 36 by 16S rRNA (V3-V4) gene amplicon sequencing and metabolic pathways were inferred with PICRUSt2 and the MetaCyc database. Data analysis and clustering were conducted with DESeq2-Wald test and hclust in R.
355 MetaCyc pathways were predicted and collapsed into 48 functional classes; 10 of these accounted for more than 80% of the total pathway relative abundance, including various biosynthetic as well as carbohydrate and protein degradation pathways. With time, 113 and 55 pathways were altered (q-values < 0.01) in the control and probiotic groups, respectively, but only control samples clustered by age. At PND 14 and 21,195 and 39 pathways were differentially represented in the probiotic group vs. controls, but none at PND 36. Age-dependent pathways altered by probiotic supplementation belonged to biosynthesis (Amino Acid, Nucleoside and Nucleotide, Cofactor, Electron Carrier, and Vitamin) and degradation (Carbohydrate, Nucleoside and Nucleotide, Secondary Metabolite Degradation, C1 Compound Utilization and Assimilation) functional classes.
Maternal probiotic supplementation accelerates the establishment of gut microbiota metabolic functions necessary to process host diet as well as for the synthesis of metabolites relevant for host health in the juvenile offspring.
NSERC; Lallemand Health Solutions; Lawson Family Chair in Microbiome Research.
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