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The role of hormones in gut–brain crosstalk is largely elusive, but recent research supports specific changes in hormone levels correlated with the gut microbiota. An interesting but unstudied area in microbial endocrinology is the interplay between the microbiota and sex hormones. The aim of this study is to investigate the effect of testosterone and sex on the mouse gut microbiome. We use in vitro experiments to test direct effects of testosterone on bacteria in fecal samples collected from male and female mice pre- and post-puberty. Sex-specific microbial and metabolic differences surrounding puberty are also examined in vivo. We then explore effects of testosterone supplementation in vivo, characterizing microbiota and metabolomes of male and female mice. We detect sex-specific differences in microbiota and associated metabolites of mice post-puberty, but in vitro experiments reveal that testosterone only affects microbiota of fecal samples collected before puberty. Testosterone supplementation in vivo affects gut microbiota and metabolomes in both male and female mice. Taking our results from in vitro and in vivo experiments, we conclude that the shift in the microbiome after puberty is at least partially caused by the higher levels of sex hormones, mainly testosterone, in the host. A study examining microbiome differences associated with puberty and sex and effects of testosterone on the microbiome in mice, finding shifts in the microbiome after puberty are partially caused by higher levels of sex hormones, mainly testosterone, in hosts. [ABSTRACT FROM AUTHOR]

• This is the first study to examine how the microbiome interacts with aggression through urine profiling. This analysis was particularly nuanced because not only did we compare basal urine metabolomes in response to microbiota manipulation (four unique study groups, above), but we also capture real-time metabolic responses to aggressive interactions by comparing samples taken before and after behavioral assays. • Here, we expanded the study of brain function in the aggression-microbiota interplay, quantifying serotonin, serotonin turnover and tryptophan levels using HPLC as well as identifying key gene expression patterns using transcriptomics in five different regions of the brain. We examined gene expression related to serotonin and other neurotransmitter receptors in multiple brain regions, identifying the septum as an important brain region for regulation of aggression. Gene set enrichment analysis was also used to highlight other, less studied pathways (Rho GTPase and Reelin) associated with aggressive behavior in the context of the gut-brain-microbiome axis. • The data generated in this study is rich (untargeted metabolomics of urine and transcriptomics of five brain regions), spanning four microbiota manipulation states, and will be publicly available , further extending the potential application of our research. • We include a study of humanized mice using unique fecal samples of 1-month-old infants, collected nearly a month after early-life ABX administration. In previous work (Uzan-Yulzari et al. 2021 , Nat Comm), we have demonstrated that ABX in this critical period of life can have lasting effects of childhood growth. Here, we extend these findings using samples from the same cohort. Using fecal samples collected weeks after ABX administration also reduces the direct chemical effects of ABX on the host, highlighting the causative role of the dysbiotic host microbiome and associated metabolome in driving aggressive behavior. We demonstrate that infant microbiota, perturbed within the first 48 h of life, has a lasting signature through 1 month of age that, when transplanted into GF mice, results in increased aggression (3 – 5 weeks after transplant) when compared to effects of stools of infants not exposed to any early-life antibiotics. The findings are revolutionary as they show how ABX-altered microbiota during a critical development window can lead to persisting behavioral deficits. Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings. Methods: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation. Results: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection. Discussion: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS. [ABSTRACT FROM AUTHOR]

Background: Giardia duodenalis (Gd) causes intestinal parasitosis. The involvement of the intestinal microbiome in determining the infection's clinical phenotype is unknown. Objective: Investigate the fecal microbiome features in dogs with giardiasis. Animals and Methods: Cross‐sectional study, including fecal samples of kenneled dogs with Gd diagnosed by fecal Giardia antigen dot ELISA. The fecal microbial compositional characteristics and dysbiosis index (DI) were compared between diarrheic and nondiarrheic dogs. Results: Fecal samples of 38 Gd‐infected dogs (diarrheic, 21; nondiarrheic, 17) were included. No differences were found in Faith's phylogenic diversity and beta diversity (weighted UniFrac distances) and in specific taxa abundances at the phylum, genus, and species levels, as well as in alpha and beta diversities between diarrheic and nondiarrheic dogs, and also when divided by sex or age. Among diarrheic dogs, alpha diversity was higher in males than in females (pairwise Kruskal‐Wallis, q = 0.01). Among males, fecal abundances of the genus Clostridium (W = 19) and Clostridium spiroforme species (W = 33) were higher in diarrheic compared to nondiarrheic dogs. In diarrheic dog fecal samples, Proteobacteria were more prevalent (W = 1), whereas Verrucomicrobia were less prevalent in dogs <1 year of age than in older dogs. The fecal sample DI of 19 diarrheic and 19 nondiarrheic dogs was similar (median, −0.2; range, −4.3 to 4.5 and median, −1.0; range, −4.3 to 5.8, respectively). Conclusions: The fecal microbial composition of symptomatic and asymptomatic dogs with giardiasis is similar. Based on fecal DI, giardiasis is not characterized by prominent dysbiosis. Other host and parasite characteristics might determine the severity of giardiasis in dogs. [ABSTRACT FROM AUTHOR]

Migration is one of the most physical and energetically demanding periods in an individual bird's life. The composition of the bird's gut or cloacal microbiota can temporarily change during migration, likely due to differences in diets, habitats and other environmental conditions experienced en route. However, how physiological condition, migratory patterns, and other drivers interact to affect microbiota composition of migratory birds is still unclear. We sampled the cloacal bacterial microbiota of a long-distance migrant, the steppe buzzard (Buteo buteo vulpinus), at an important spring stopover bottleneck in Eilat, Israel, after crossing the ca. 1800 km Sahara Desert. We examined whether diversity and composition of the cloacal microbiota varied with body condition, sex, movement patterns (i.e., arrival time and migration distance), and survival. Early arrival to Eilat was associated with better body condition, longer post-Eilat spring migration distance, higher microbial α-diversity, and differences in microbiota composition. Specifically, early arrivals had higher abundance of the phylum Synergistota and five genera, including Jonquetella and Peptococcus, whereas the phylum Proteobacteria and genus Escherichia-Shigella (as well as three other genera) were more abundant in later arrivals. While the differences in α-diversity and Escherichia-Shigella seem to be mainly driven by body condition, other compositional differences associated with arrival date could be indicators of longer migratory journeys (e.g., pre-fueling at wintering grounds or stopover habitats along the way) or migratory performance. No significant differences were found between the microbiota of surviving and non-surviving individuals. Overall, our results indicate that variation in steppe buzzard microbiota is linked to variation in migratory patterns (i.e., capture/arrival date) and body condition, highlighting the importance of sampling the microbiota of GPS-tracked individuals on multiple occasions along their migration routes to gain a more detailed understanding of the links between migration, microbiota, and health in birds. [ABSTRACT FROM AUTHOR]

The microbiome influences the emotional and cognitive phenotype of its host, as well as the neurodevelopment and pathophysiology of various brain processes and disorders, via the well‐established microbiome–gut–brain axis. Rapidly accumulating data link the microbiome to severe neuropsychiatric disorders in humans, including schizophrenia, Alzheimer's and Parkinson's. Moreover, preclinical work has shown that perturbation of the microbiome is closely associated with social, cognitive and behavioural deficits. The potential of the microbiome as a diagnostic and therapeutic tool is currently undercut by a lack of clear mechanistic understanding of the microbiome–gut–brain axis. This review establishes the hypothesis that the mechanism by which this influence is carried out is synaptic plasticity – long‐term changes to the physical and functional neuronal structures that enable the brain to undertake learning, memory formation, emotional regulation and more. By examining the different constituents of the microbiome–gut–brain axis through the lens of synaptic plasticity, this review explores the diverse aspects by which the microbiome shapes the behaviour and mental wellbeing of the host. Key elements of this complex bi‐directional relationship include neurotransmitters, neuronal electrophysiology, immune mediators that engage with both the central and enteric nervous systems and signalling cascades that trigger long‐term potentiation of synapses. The importance of establishing mechanistic correlations along the microbiome–gut–brain axis cannot be overstated as they hold the potential for furthering current understanding regarding the vast fields of neuroscience and neuropsychiatry. This review strives to elucidate the promising theory of microbiome‐driven synaptic plasticity in the hope of enlightening current researchers and inspiring future ones. [ABSTRACT FROM AUTHOR]

Treatment We have described how microbiota and metabolite profiles can be used to diagnose diseases, predict future onset and even predict treatment success rates. Over the coming years, researchers should be able to exploit pharmacomicrobiomics not only to increase treatment efficacy but also to reduce unwanted side effects of therapeutics, making treatments with potentially debilitating side effects in a subset of the population more palatable and raising the appeal of treatments like antipsychotics, and even birth control, to individuals who are extremely hesitant because of associated weight gain. 67 Zheng, Y.-Y., Wu, T.-T., Liu, Z.-Q., Li, A., Guo, Q.-Q., Ma, Y.-Y., et al. (2020) Gut microbiome-based diagnostic model to predict coronary artery disease. Accordingly, current research points to the utility of microbiota screening when planning treatment for a range of diseases, and a standardized ML model that accounts for patient characteristics, disease expression and microbiota composition could change the way we approach disease treatment. [Extracted from the article]

Human activities shape resources available to wild animals, impacting diet and probably altering their microbiota and overall health. We examined drivers shaping microbiota profiles of common cranes (Grus grus) in agricultural habitats by comparing gut microbiota and crane movement patterns (GPS‐tracking) over three periods of their migratory cycle, and by analysing the effect of artificially supplemented food provided as part of a crane‐agriculture management programme. We sampled faecal droppings in Russia (nonsupplemented, premigration) and in Israel in late autumn (nonsupplemented, postmigration) and winter (supplemented and nonsupplemented, wintering). As supplemented food is typically homogenous, we predicted lower microbiota diversity and different composition in birds relying on supplementary feeding. We did not observe changes in microbial diversity with food supplementation, as diversity differed only in samples from nonsupplemented wintering sites. However, both food supplementation and season affected bacterial community composition and led to increased abundance of specific genera (mostly Firmicutes). Cranes from the nonsupplemented groups spent most of their time in agricultural fields, probably feeding on residual grain when available, while food‐supplemented cranes spent most of their time at the feeding station. Thus, nonsupplemented and food‐supplemented diets probably diverge only in winter, when crop rotation and depletion of anthropogenic resources may lead to a more variable diet in nonsupplemented sites. Our results support the role of diet in structuring bacterial communities and show that they undergo both seasonal and human‐induced shifts. Movement analyses provide important clues regarding host diet and behaviour towards understanding how human‐induced changes shape the gut microbiota in wild animals. [ABSTRACT FROM AUTHOR]

The gut microbiota refers to an entire population of microorganisms that colonize the gut. This community includes viruses, prokaryotes (bacteria and archaea), and eukaryotes (fungi and parasites). Multiple studies in the last decades described the significant involvement of gut bacteria in gut-brain axis communication; however, the involvement of other members of the gut microbiota has been neglected. Recent studies found that these 'forgotten' members of the gut microbiota may also have a role in gut-brain communication, although it is still unclear whether they have a direct effect on the brain or if their effects are mediated by gut bacteria. Here, we provide concrete suggestions for future research to tease out mechanisms of the microbiota-gut-brain axis. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies". • Many studies show that non-bacterial members have an impact on bacterial community composition and function. • There is growing evidence that fungi, viruses, parasites, and archaea in the gastrointestinal tract have an influence on the gut-brain axis. • It is still unclear whether the 'forgotten' members directly affect the brain or if their effects are mediated by gut bacteria. [ABSTRACT FROM AUTHOR]

In an era in which protein consumption is enthusiastically advocated, this work explored the possible formation of proteinaceous amyloids in foods and their unchartered digestive fate. Evidence herein corroborates processing induces formation of amyloid-like architectures from β-lactoglobulin or ovalbumin. Such supramolecular assemblies exhibit attenuated susceptibility to gastric and intestinal proteolysis and may persist into the colon as confirmed by SDS-PAGE, LCMS, ThT analysis and TEM imaging. Human fecal fermentations of fibrils or their native protein counterparts establish that fibrilization helps maintain microbial diversity, low Firmicutes/Bacteroidetes ratio (Av. F/B ratio<3.00) and protect the butyrate producing genera Roseburia and Clostridium. In addition, fibrilization increased the minimal inhibitory concentration (MIC) of ovalbumin by at least two orders of magnitude without altering its negligible cytotoxicity. Further, In silico analyses support that both fibrils divert predicted microbiota metabolic trajectories towards those observed in fermentation of prebiotics. Thus, this work provides reassuring evidence against possible adverse effects of fibrilization of edible proteins. Yet, human trials with processed foods should be warranted to clinically affirm these findings. [Display omitted] • Amyloid fibrils from β-lactoglobulin and ovalbumin show attenuated digestive breakdown. • Human fecal fermentations show fibrils support low Firmicutes to Bacteroidetes ratios. • BLG fibrils show no differential fermentability compared to BLG. • OVA fibrils abolish the adverse antimicrobial effects of OVA on gut microbiota. • Roseburia and Clostridium symbiotic taxa are affected and diverse impact on metabolic pathways is predicted in silico. [ABSTRACT FROM AUTHOR]

The composition of the gut microbiome is greatly influenced by nutrition and dietary alterations which can also induce large temporary microbial shifts. However, the molecular mechanisms that promote these changes remain to be determined. Species of the family Lactobacillaceae and Bacillus species are genetically manipulatable bacteria that are naturally found in the human gastrointestinal (GI) tract and are often considered models of beneficial microbiota. Here, we identify specific conserved molecular pathways that play a key role in host colonization by beneficial members of the microbiota. In particular, we highlight three pathways important to the success of lactic acid bacteria (LAB) in the GI tract: glycolysis and fermentation, microbial communication via membrane vesicles, and condition-dependent antibiotic production. We elaborate on how the understanding of these circuits can lead to the development of novel therapeutic approaches to combat GI tract infections. The activities of probiotic communities under different environmental conditions can be predicted. Fermentation capacity and acid tolerance are good predictors of probiotic communities' structure and function for members of the Lactobacillaceae. Adhesion, quorum sensing, and membrane vesicle formation are potential predictors of the success of probiotic communities, but their regulators remain to be determined. Antibiotic production and delivery are governed by fermentation, quorum sensing, and membrane vesicle formation. Certain beneficial functions of lactic-acid-positive bacteria can be mimicked by purified self-produced antibiotics and membrane vesicles. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24–28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300 m buffer had lower odds of GDM (OR = 0.45, 95% CI: 0.16, 1.26, p = 0.13) and decreased change in mean glucose levels (β = −6.28, 95% CI: 14.91, 2.24, p = 0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500 m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations. [Display omitted] • Gestational diabetes mellitus (GDM) and greenness were previously associated. • GDM was also previously associated with reduced gut microbiota richness. • Microbiome richness was evaluated by 4 alpha indices in stool and saliva samples. • Possible associations between residential greenness and risk of GDM were observed. • Microbiome richness does not mediate this possible association. [ABSTRACT FROM AUTHOR]