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Turjeman, S.

Publications and source records attributed to Turjeman, S..

11 recordsLinked to original sources

Barking up the microbiome tree: a multi-body-site characterization of maternal postpartum and pup early colonization dynamics

Early-life microbial colonization is critical for shaping host development, yet how different maternal microbial reservoirs contribute to colonization of distinct offspring body sites remains poorly understood. Here, we explored microbial colonization and maturation of oral and rectal microbiota in puppies during the first postnatal week and assessed the contributions of maternal oral, vaginal, rectal, and milk microbiota to early colonization. We collected 505 samples from 33 dams and their litters at day 1 and day 8 postpartum and characterized microbial communities using 16S rRNA gene sequencing. We found that the pup oral microbiome on day 1 closely resembled maternal milk and vaginal microbiota. In contrast, the pup rectal microbiome was initially distinct from all maternal body sites, suggesting contributions from additional unmeasured sources. By day 8, both oral and rectal microbiomes exhibited signs of early maturation, with decreased relative abundance of opportunistic taxa and increased resemblance to maternal profiles. In dams, the vaginal microbiome showed the largest postpartum shift, while the rectal microbiome exhibited a smaller but significant change, and milk and oral microbiomes remained stable. Our results reveal that maternal contributions to early microbiome assembly are body-site specific, with oral and rectal microbiomes following distinct developmental trajectories during the first week of life, consistent with a dynamic colonization process shaped by both maternal and likely additional non-maternal sources. The observed patterns parallel those reported in humans, supporting the value of dogs as a comparative model for studying early-life microbiome colonization and maternal-offspring transmission in mammals.

microbiology↗

From parental antibiotics to offspring locomotion: L-norvaline links microbiome disruption to intergenerational reprogramming in Drosophila

The maternal microbiome during oogenesis is a critical but underappreciated regulator of offspring physiology. Using Drosophila melanogaster as a model, we show that a single, transient antibiotic exposure during oogenesis, without direct offspring exposure, is sufficient to reprogram larval behaviour, gene expression, and metabolism. Adult flies exposed to either ciprofloxacin or vancomycin produced third-instar larvae with significantly reduced crawling speed and a significantly higher prevalence of abnormal locomotion. Transcriptomic profiling revealed widespread downregulation of genes governing energy metabolism, particularly the tricarboxylic acid cycle, as well as cuticle development and protein folding. Metabolomic profiling identified elevation of L-norvaline across both antibiotic groups, and acute parental supplementation with L-norvaline alone recapitulated the observed crawling deficits, directly implicating this metabolite in the phenotype. These findings demonstrate that even brief disruption of the microbiome during oogenesis triggers a cascade of intergenerational physiological changes, establishing this window as a key period of microbiome-dependent offspring programming.

microbiology↗

Nutrition-dependent development of the Oral Microbiome in Early Pregnancy

BackgroundMost studies of the oral microbiome during pregnancy have focused on the second and third trimesters (T2, T3, respectively). Findings remain inconsistent-some report shifts in specific taxa, whereas others observe little change in diversity. To date, no large-scale longitudinal study has examined oral microbiome development across all three trimesters, leaving early gestational dynamics (during the first trimester; T1) largely unexplored. MethodsWe conducted a longitudinal analysis of the oral microbiome in 346 pregnant women from Israel and validated key findings in an independent cohort of 154 pregnant women from Russia. In Israel, saliva samples were collected during T1 (11-14 weeks), T2 (24-28 weeks), and T3 (32-38 weeks) trimesters; in Russia, samples were collected during T2 and T3 with similar ranges of gestational weeks. Alongside sample collection, participants completed dietary and health questionnaires to assess maternal factors that could influence microbial composition. Microbial profiles were analyzed to test for (i) differential abundance across trimesters and (ii) the influence of maternal nutrition and lifestyle factors on these dynamics. ResultsSignificant shifts in oral microbial composition were observed as early as the transition from T1 to T2. Alpha diversity decreased progressively across pregnancy (Shannon index: T1 = 3.261, T2 = 3.173, T3 = 3.109; Kruskal-Wallis p = 0.0023). Notable taxonomic changes included a significant reduction in Verrucomicrobiota (particularly Akkermansia muciniphila) and an increase in Synergistota from T1 to T2 (adjusted p < 0.01), alongside an increase in Gammaproteobacteria and a decrease in Erysipelotrichia, suggesting an ecological shift towards potentially pro-inflammatory communities. Despite these systematic population-level changes, within-subject microbial distances across trimesters were smaller than between-subject distances, indicating that individual women maintained relatively stable microbial profiles over time. Among 54 maternal variables examined, gluten-free diet showed the strongest and most consistent associations with oral microbiome composition across all trimesters, followed by smoking history and conception method. Key findings were validated in an independent cohort of 154 Russian women. ConclusionsThis study provides the first large-scale evidence of significant oral microbiome changes beginning in early pregnancy, characterized by reduced diversity and a directional shift toward potentially pro-inflammatory communities. The strong associations with gluten consumption and smoking suggest a large-scale effect of lifestyle on the pregnancy oral microbiome. The alteration in the microbial composition highlights the oral microbiome as a sensitive marker of gestational physiology.

microbiology↗

Aggression: A gut reaction? The effects of gut microbiome on aggression

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. In our investigation, we meticulously examined the behavioral patterns of four groups of mice - wild-type, germ-free (GF), mice treated with antibiotics, and recolonized GF mice - to gain mechanistic insights into the impact of the gut microbiome on aggression. We discovered a significant correlation between diminished microbiome and increased aggression. Importantly, this behavioral shift could be restored when a WT microbiota was reinstated. Microbiota manipulation also significantly altered brain function, particularly in aggression-associated genes, and urine metabolite profiles. Notably, our study extends beyond the murine model, shedding light on clinical implications of early-life antibiotic exposure. We found that fecal microbiome transplants from 1mo old infants prescribed antibiotics during their first days of life led to a marked increase in aggression in recipient mice. This research demonstrates that the microbiota modulates aggression and underscores its importance in the realm of behavioral science. One-Sentence SummaryThe antibiotic-altered gut microbiome is implicated in increased aggression. It also leads to altered brain function, particularly in genes linked to aggression, and urine metabolite profiles showing a multi-system response to microbiota disruption.

animal behavior and cognition↗

Bacteroides is increased in an autism cohort and induces autism-relevant behavioral changes in mice in a sex-dependent manner

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which is defined by decreased social communication and the presence of repetitive or stereotypic behaviors. Recent evidence has suggested that the gut-brain axis may be important in neurodevelopment in general and may play a role in ASD in particular. Here, we present a study of the gut microbiome in 96 individuals diagnosed with ASD in Israel, compared to 42 neurotypical individuals. We determined differences in alpha and beta diversity in the microbiome of individuals with ASD and demonstrated that the phylum Bacteroidetes and genus Bacteroides were the most significantly over-represented in individuals with ASD. To understand the possible functional significance of these changes, we treated newborn mice with Bacteroides fragilis at birth. B. fragilis-treated male mice displayed social behavior dysfunction, increased repetitive behaviors and gene expression dysregulation in the prefrontal cortex, while female mice did not display behavioral deficits. These findings suggest that overabundance of Bacteroides, particularly in early life, may have functional consequences for individuals with ASD.

neuroscience↗

An experimental approach towards untangling the role of nature versus nurture in shaping the microbiome of social insects

The gut microbiota is intimately related to host wellbeing, in terms of physiology, immune function, and even social interactions. The strength of this relationship is dynamic, but the extent to which the microbiome is shaped by the identity of the host (nature) or its environment (nurture) remains largely unknown. Here we aimed to identify factors shaping the microbiomes of nursing workers and larvae of two Vespidae species, using a cross-species experimental design to control for effects of environment, host identity and their interactions. We found that the microbiome composition of adults depended principally on the environment. Conversely, larval microbiome composition differed more between host species, regardless of treatment. We also found distinct microbiota profiles between the two species, across life stages and independently. These findings further elucidate the complexity of the host-microbiome relationship shaped by the environment while retaining symbionts that benefit the host. These results suggest that holobiont evolution may have promoted the rise of social behavior in animals.

evolutionary biology↗

Metabolic rewiring of the probiotic bacterium Lacticaseibacillus rhamnosus GG contributes to cell wall remodeling and antimicrobials production

Lacticaseibacillus rhamnosus GG (LGG) is a Gram-positive beneficial bacterium that resides in the human intestinal tract and belongs to the family of lactic acid bacteria (LAB). This bacterium is a widely used probiotic and was suggested to provide numerous benefits for human health. However, as in most LAB strains, the molecular mechanisms that mediate the competitiveness of probiotics under different diets remain unknown. Fermentation is a fundamental process in LAB, allowing the oxidation of simple carbohydrates (e.g., glucose, mannose) for energy production under conditions of oxygen limitation, as in the human gut. Our results indicate that fermentation reshapes the metabolome, volatilome, and proteome architecture in LGG. Furthermore, fermentation alters cell envelope remodeling and peptidoglycan biosynthesis, which leads to altered cell wall thickness, aggregation properties, and cell wall composition. In addition, fermentable sugars induced secretion of known and novel metabolites and proteins targeting the enteric pathogens Enterococcus faecalis and Salmonella Enterica serovar Typhimurium. Overall, our results link the common metabolic regulation of cell wall remodeling, aggregation to host tissues, biofilm formation in probiotic strains, and connect the production of antimicrobial effectors with metabolome reprogramming. These findings provide novel insights into the role of nutrition in the establishment of LGG in the gastrointestinal tract.

microbiology↗

Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress

Colonic goblet cells are specialized epithelial cells that secrete mucus to form a barrier between the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 led to production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, inhibiting Beclin 1-induced autophagy via Bcl-2 impaired mucus secretion. Furthermore, alleviating intestinal ER stress with a bile acid, or activating the unfolded protein response (UPR) pharmacologically via eIF2 phosphorylation, led to excessive mucus production. Over-production of mucus altered the gut microbiome, with expansion of mucus-utilizing bacteria, and protected from intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, while autophagy maintains proper mucus secretion and intestinal homeostasis by relieving ER stress.

immunology↗

Noninvasive sampling for comparisons of wildlife microbiomes may be more reliable than sampling trapped animals

In ecological and conservation studies, responsible researchers strive to obtain rich data while minimizing disturbance to wildlife and ecosystems. We assessed if samples collected noninvasively can be used for microbiome research, comparing microbiota of noninvasively collected fecal samples to those collected from trapped common cranes at the same sites over the same periods. We found significant differences in microbial composition (alpha and beta diversity), which were not accounted for by noninvasive samples exposure to soil contaminants, as manually assessed by comparing differentially abundant taxa. They could result from trapped birds exposure to sedatives. We conclude that if all samples are collected in the same manner, comparative analyses are valid, and noninvasive sampling may better represent host microbiota because there are no trapping effects. Experiments with fresh and delayed sample collection can elucidate effects of environmental exposures on microbiota. Further, stressing or sedation may unravel how trapping affects wildlife microbiota.

ecology↗

Progesterone supplementation in mice leads to microbiome alterations and weight gain in a sex-specific manner

BackgroundProgesterone is a steroid hormone produced by the ovaries, involved in pregnancy progression and necessary for successful gestation. We have previously shown that progesterone affects gut microbiota composition and leads to increased relative abundance of Bifidobacterium. ResultsIn non-pregnant female GF mice, levels of progesterone were significantly higher than in SPF mice of the same status. However, no significant differences were observed between GF and SPF males. Females treated with progesterone gained more weight than females treated with a placebo. In contrast to female mice, males treated with progesterone did not gain significantly more weight than males treated with a placebo. Progesterone supplementation led to microbial changes in females but not in males (16S rRNA sequencing). Accordingly, the weight gain observed in female mice treated with progesterone was fully transferable to both male and female germ-free mice via fecal transplantation. ConclusionsWe demonstrate that bacteria play a role in regulating progesterone levels in a female-specific manner. Furthermore, weight gain and metabolic changes associated with progesterone may be mediated by the gut microbiota.

microbiology↗

Antibiotics increase aggression behavior and aggression-related pheromones and receptors in Drosophila melanogaster

Aggression is a behavior common in most species; it is controlled by internal and external drivers, including hormones, environmental cues, and social interactions, and underlying pathways are understood in a broad range of species. To date, though, effects of gut microbiota on aggression in the context of gut-brain communication and social behavior have not been elucidated. We examine how manipulation of Drosophila melanogaster microbiota affect aggression as well as the pathways that underly the behavior in this species. Flies treated with antibiotics exhibited significantly more aggressive behaviors. Furthermore, they had higher levels of vCA and (Z)-9 Tricosene, pheromones associated with aggression in flies, as well as higher expression of the relevant pheromone receptors and transporters OR67d, OR83b, GR32a, and LUSH. These findings suggest that aggressive behavior is, at least in part, mediated by bacterial species in flies.

microbiology↗