Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells.

Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play a critical role in resistance to immunotherapy. In this study, we identified epidermal growth factor-like 6 (Egfl6) as a regulator of myeloid cell functions. Our analyses indicated that Egfl6, via binding with β3 integrins and activation of p38 and SYK signaling, acts as a chemotactic factor for myeloid cell migration and promotes their differentiation toward an immunosuppressive state.

Diet influences community dynamics following vaginal group B streptococcus colonization.

The vaginal microbiota plays a pivotal role in reproductive, sexual, and perinatal health and disease. Unlike the well-established connections between diet, metabolism, and the intestinal microbiota, parallel mechanisms influencing the vaginal microbiota and pathogen colonization remain overlooked. In this study, we combine a mouse model of strain COH1 [group B (GBS)] vaginal colonization with a mouse model of pubertal-onset obesity to assess diet as a determinant of vaginal microbiota composition and its role in colonization resistance.

Rapid modeling of an ultra-rare epilepsy variant in wild-type mice by in utero prime editing.

Generating animal models for individual patients within clinically-useful timeframes holds great potential toward enabling personalized medicine approaches for genetic epilepsies. The ability to rapidly incorporate patient-specific genomic variants into model animals recapitulating elements of the patient's clinical manifestations would enable applications ranging from validation and characterization of pathogenic variants to personalized models for tailoring pharmacotherapy to individual patients. Here, we demonstrate generation of an animal model of an individual epilepsy patient with an ultra-rare variant of the NMDA receptor subunit GRIN2A, without the need for germline transmission and breeding.

Intestinal microbial circadian rhythms drive sex differences in host immunity and metabolism.

Circadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific intestinal microbial circadian rhythms in host metabolism using germ-free and conventionalized mice and manipulation of dietary-derived fat, fiber, and microbiota-accessible carbohydrates. Our findings demonstrate that sex differences in circadian rhythms of genes involved in immunity and metabolism depend on oscillations in microbiota, microbial metabolic functions, and microbial metabolites.

Perinatal exposure to tetracycline contributes to lasting developmental effects on offspring.

Background: For more than 30 years, the tetracycline on/off system of inducible gene expression has been leveraged to study disease mechanisms across many research areas, especially that of metabolism and neuroscience. This system requires acute or chronic exposure to tetracycline derivatives, such as doxycycline, to manipulate gene expression in a temporal and tissue-specific manner, with exposure often being restricted to gestational and early developmental windows. Despite evidence showing that early life antibiotic exposure has adverse effects on gut microbiota, metabolism, physiology, immunity and behavior, little is known regarding the lasting impact of doxycycline treatment on relevant outcomes in experimental offspring.

Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress.

Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex bias in susceptibility, presentation, onset, and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes.

Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment.

Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis.

It's the fiber, not the fat: significant effects of dietary challenge on the gut microbiome.

Background: Dietary effects on the gut microbiome play key roles in the pathophysiology of inflammatory disorders, metabolic syndrome, obesity, and behavioral dysregulation. Often overlooked in such studies is the consideration that experimental diets vary significantly in the proportion and source of their dietary fiber. Commonly, treatment comparisons are made between animals fed a purchased refined diet that lacks soluble fiber and animals fed a standard vivarium-provided chow diet that contains a rich source of soluble fiber.

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression.

Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear.

Prenatal and postnatal contributions of the maternal microbiome on offspring programming.

The maternal microbiota is positioned to regulate the development of offspring immunity, metabolism, as well as brain function and behavior. The mechanisms by which maternal microbial signals drive these processes are beginning to be elucidated. In this review, we provide a brief overview on the importance of the microbiome in brain function and behavior, define the maternal vaginal and gut microbiota as distinct influences on offspring development, and outline current concepts in microbial origins of offspring health outcomes.

Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy.

Background: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes.

The maternal vaginal microbiome partially mediates the effects of prenatal stress on offspring gut and hypothalamus.

Early prenatal stress disrupts maternal-to-offspring microbiota transmission and has lasting effects on metabolism, physiology, cognition, and behavior in male mice. Here we show that transplantation of maternal vaginal microbiota from stressed dams into naive pups delivered by cesarean section had effects that partly resembled those seen in prenatally stressed males. However, transplantation of control maternal vaginal microbiota into prenatally stressed pups delivered by cesarean section did not rescue the prenatal-stress phenotype.

Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner.

The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by altering the temporal and spatial dynamics of the maternal microbiome during pregnancy.

Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish.

The consumption of probiotics has become increasingly popular as a means to try to improve health and well-being. Not only are probiotics considered beneficial to digestive health, but increasing evidence suggests direct and indirect interactions between gut microbiota (GM) and the central nervous system (CNS). Here, adult zebrafish were supplemented with Lactobacillus plantarum to determine the effects of probiotic treatment on structural and functional changes of the GM, as well as host neurological and behavioral changes.

Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk.

Sex differences in the gut microbiome-brain axis across the lifespan.

In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals.

Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring.

A novel role for maternal stress and microbial transmission in early life programming and neurodevelopment.

Perturbations in the prenatal and early life environment can contribute to the development of offspring stress dysregulation, a pervasive symptom in neuropsychiatric disease. Interestingly, the vertical transmission of maternal microbes to offspring and the subsequent bacterial colonization of the neonatal gut overlap with a critical period of brain development. Therefore, environmental factors such as maternal stress that are able to alter microbial populations and their transmission can thereby shape offspring neurodevelopment.

Dissociable effects of dorsal and ventral hippocampal DHA content on spatial learning and anxiety-like behavior.

Chronic deficiency of dietary docosahexaenoic acid (DHA) during critical developmental windows results in severe deficits in spatial learning, anxiety and hippocampal neuroplasticity that parallel a variety of neuropsychiatric disorders. However, little is known regarding the influence of long-term, multigenerational exposure to dietary DHA enrichment on these same traits. To characterize the potential benefits of multigenerational DHA enrichment, mice were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 0.

Patient satisfaction with primary care: are there differences between the approaches in family and general medicine?

Aim: To examine patients' satisfaction with health care services in primary care, and to determine a difference of attitudes towards the work of general and family medicine offices.

Methods: This descriptive analytical study was conducted among patients of the Primary Health Care Zenica, who had had recent experience with the work of family or general medicine. The questionnaire for the evaluation of general and family medicine by patients was made on the basis of standardized European Project on Patient Evaluation of General Practice Care questionnaires (EUROPEP).

Sexually selected traits: a fundamental framework for studies on behavioral epigenetics.

Emerging evidence suggests that epigenetic-based mechanisms contribute to various aspects of sex differences in brain and behavior. The major obstacle in establishing and fully understanding this linkage is identifying the traits that are most susceptible to epigenetic modification. We have proposed that sexual selection provides a conceptual framework for identifying such traits.

Effects of developmental bisphenol A exposure on reproductive-related behaviors in California mice (Peromyscus californicus): a monogamous animal model.

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist-antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females.