Transgenerational effects of early life stress on the fecal microbiota in mice.

Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life, including abundance of eight amplicon sequencing variants (ASVs). Further effects on fecal microbial composition, structure (weighted Jaccard index), and abundance of 16 ASVs are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring.

GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance.

The high neuroactive potential of metabolites produced by gut microbes has gained traction over the last few years, with metagenomic-based studies suggesting an important role of microbiota-derived γ-aminobutyric acid (GABA) in modulating mental health. Emerging evidence has revealed the presence of the glutamate decarboxylase (GAD)-encoding gene, a key enzyme to produce GABA, in the prominent human intestinal genus Bacteroides. Here, we investigated GABA production by Bacteroides in culture and metabolic assays combined with comparative genomics and phylogenetics. A total of 961 Bacteroides genomes were analyzed in silico and 17 metabolically and genetically diverse human intestinal isolates representing 11 species were screened in vitro. Using the model organism Bacteroides thetaiotaomicron DSM 2079, we determined GABA production kinetics, its impact on milieu pH, and we assessed its role in mitigating acid-induced cellular damage. We showed that the GAD-system consists of at least four highly conserved genes encoding a GAD, a glutaminase, a glutamate/GABA antiporter, and a potassium channel. We demonstrated a high prevalence of the GAD-system among Bacteroides with 90% of all Bacteroides genomes (96% in human gut isolates only) harboring all genes of the GAD-system and 16 intestinal Bacteroides strains producing GABA in vitro (ranging from 0.09 to 60.84 mM). We identified glutamate and glutamine as precursors of GABA production, showed that the production is regulated by pH, and that the GAD-system acts as a protective mechanism against acid stress in Bacteroides, mitigating cell death and preserving metabolic activity. Our data also indicate that the GAD-system might represent the only amino acid-dependent acid tolerance system in Bacteroides. Altogether, our results suggest an important contribution of Bacteroides in the regulation of the GABAergic system in the human gut.

Traditional milk transformation schemes in Côte d'Ivoire and their impact on the prevalence of Streptococcus bovis complex bacteria in dairy products.

The Streptococcus bovis/Streptococcus equinus complex (SBSEC) and possibly Streptococcus infantarius subsp. infantarius (Sii) are associated with human and animal diseases. Sii predominate in spontaneously fermented milk products with unknown public health effects. Sii/SBSEC prevalence data from West Africa in correlation with milk transformation practices are limited. Northern Côte d'Ivoire served as study area due to its importance in milk production and consumption and to link a wider Sudano-Sahelian pastoral zone of cross-border trade. We aimed to describe the cow milk value chain and determine Sii/SBSEC prevalence with a cross-sectional study. Dairy production practices were described as non-compliant with basic hygiene standards. The system is influenced by secular sociocultural practices and environmental conditions affecting product properties. Phenotypic and molecular analyses identified SBSEC in 27/43 (62.8%) fermented and 26/67 (38.8%) unfermented milk samples. Stratified by collection stage, fermented milk at producer and vendor levels featured highest SBSEC prevalence of 71.4% and 63.6%, respectively. Sii with 62.8% and 38.8% as well as Streptococcus gallolyticus subsp. macedonicus with 7.0% and 7.5% were the predominant SBSEC species identified among fermented and unfermented milk samples, respectively. The population structure of Sii/SBSEC isolates seems to reflect evolving novel dairy-adapted, non-adapted and potentially pathogenic lineages. Northern Côte d'Ivoire was confirmed as area with high Sii presence in dairy products. The observed production practices and the high diversity of Sii/SBSEC supports in-depth investigations on Sii ecology niche, product safety and related technology in the dairy value chain potentially affecting large population groups across sub-Saharan Africa.

Risk factors for the carriage of Streptococcus infantarius subspecies infantarius isolated from African fermented dairy products.

Streptococcus infantarius subsp. infantarius (Sii) has been identified as predominant lactic acid bacteria in spontaneously fermented dairy products (FDPs) in sub-Saharan Africa including Côte d'Ivoire. However, Sii belongs to the Streptococcus bovis/Streptococcus equinus complex (SBSEC). Most SBSEC members are assumed to be involved as opportunistic pathogens in serious diseases in both humans and animals. A population-based cross-sectional survey, including 385 participants was conducted in Korhogo, northern Côte d'Ivoire, to identify risk factors for Sii fecal carriage, including consumption of local FDPs. A structured questionnaire was used to gather participant's socio-demographic and economic characteristics, their relation to livestock and dietary habits. In addition, fresh stool and milk samples were collected. The identification of Sii was done using a SBSEC-specific PCR assay targeting 16S rRNA and groEL genes. The overall prevalence of SBSEC and Sii carriage was 23.2% (confidence interval CI 95% = 18.9-27.5) and 12.0% (CI 95% = 8.4-15.5) for stool, respectively. Prevalence of Sii was significantly higher in consumers of artisanal butter compared with non-consumers (57.1% vs 10.1%, odds ratio OR: 11.9, 95% CI: 3.9-36.6), as well as in persons handling livestock (OR = 3.9; 95% CI = 1.6-9.3) and livestock primary products (OR = 5.7; 95% CI = 2.3-14.3). The closer contact with livestock was a risk factor for Sii fecal carriage. Sii strains were isolated from fresh and fermented milk products with a prevalence of 30.4% and 45.4%, respectively. Analysis of Sii population structure through the SBSEC multi locus sequence typing assay revealed a close relationship across human and dairy isolates, possibly linked to a Kenyan human isolate. All these outcomes underline the interest of in-depth investigations on the ecology, potential reservoirs and pathways of contamination by Sii at the human-animal-environment interface in comparison to yet to be collected data from Europe, Asia and the Americas to further elucidate the various roles of Sii.

Colorectal cancer-associated Streptococcus infantarius subsp. infantarius differ from a major dairy lineage providing evidence for pathogenic, pathobiont and food-grade lineages.

Streptococcus infantarius subsp. infantarius (Sii), a member of the Streptococcus bovis/Streptococcus equinus complex (SBSEC), predominates as dairy-adapted and non-adapted variants in fermented dairy products (FDP) in East and West Africa. Epidemiologic data suggest an association with colorectal cancer for most SBSEC members, including Sii from Kenyan patients. Phylogenetic relationships of East African human (EAH) isolates to those of dairy and pathogenic origin were analysed to better estimate potential health implications via FDP consumption. The MLST-derived population structure was also evaluated to provide host, disease, geography and dairy adaptation associations for 157 SBSEC isolates, including 83 novel Sii/SBSEC isolates of which 40 originated from Kenyan colonoscopy patients. Clonal complex (CC) 90 was delineated as potential pathogenic CC for Sii. Single EAH, West African dairy (WAD), food and animal Sii isolates clustered within CC-90, suggesting a potential link to pathogenic traits for CC-90. The majority of EAH and WAD Sii were clustered in a shared clade distinct from CC-90 and East African dairy (EAD) isolates. This indicates shared ancestry for the EAH and WAD clade and limitations to translate disease associations of EAH and CC-90 to EAD Sii, which could support the separation of pathogenic, pathobiont/commensal and food lineages.