The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.

Depression seriously affects people's quality of life, and there is an urgent need to find novel drugs to cure treatment-resistant depression. Berberine (BBR), extracted from Coptis chinensis Franch., Phellodendron bark, Berberis vulgaris, and Berberis petiolaris, could be a potential multi-target drug for depression. To summarize the effects of BBR on depression in terms of in vitro or in vivo experiments, we searched electronic databases, such as PubMed, Web of Science, Google Scholar, Wanfang Database, and China National Knowledge Infrastructure, from inception until May 2024. Then, we summarize that BBR has indirect antidepressant properties to improve depressive symptoms, manifesting in modulating the gut microbial community, strengthening the intestinal barrier, increasing the abundance of short-chain fatty acid-producing bacteria, and regulating tryptophan metabolism. BBR also exerts antidepressant-like effects via remodulating nuclear factor-erythroid 2-related factor 2/antioxidant response element pathway, hypothalamic-pituitary-adrenal axis, and peroxisome proliferators-activated receptor-delta. Nevertheless, further clinical trials and more high-quality animal studies are needed to show the actual clinical value of BBR for depression.

Stress is closely related to life, and it can also cause many mental disorders. However, there are significant sex differences in neuropsychiatric disorders associated with stress, particularly in depression, where the lifetime risk of depression in women is approximately twice that of men. However, the specific mechanism of this process has not been explained in detail.

Chronic restraint stress (CRS) + chronic and unpredictable mild stress (CUMS) was used to simulate social stress, and behavioral experiments, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, and metabolomics analysis of hippocampal and intestinal contents were performed.

The results showed that stress induced anxiety-like behavior in female mice and depression-like behavior in male mice. Sex differences in behavior may be related to monoamine neurotransmitters, hyperactivity of HPA axis, inflammatory factors, gut microbiota, and brain-gut metabolism. It is worth noting that stress caused opposite trends in DA (dopamine) levels, abundance of f-lactobaciliaceae, and levels of metabolites (1, 2-distearoyl-SN-glycero-3-phosphocholine) and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z)) in male and female mice.

The difference in neurotransmitter levels, the disorder of gut microbiota, and the abnormal brain and gut metabolism may lead to the gender difference in stress behavior.

Menopause is characterized by the cessation of menstruation and a decline in reproductive function, which is an intrinsic component of the aging process. However, it has been a frequently overlooked field of women's health. The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. Therefore, a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota. Our study elucidates the complex interplay between the microbiome and sex hormone levels, explores microbial crosstalk dynamics, and investigates the associations between the microbiome and diseases linked to menopause. Additionally, this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases. Given that menopause can last for approximately 30 years, gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions, which may result in symptomatic relief from menopause and an increase in quality of life in women.

Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.

Perimenopausal depression is a psychiatric disorder that occurs around the time of menopause and seriously affects women's health. The pathogenesis of perimenopausal depression is unclear which affects its prevention and treatment. Quercetin is a flavonoid compound with antidepressant and estrogen-like effects. The aim of this research was to investigate the role of quercetin on adrenal gland metabolic disorders in perimenopausal depressed rats based on untargeted metabolomics. Female Wistar rats with no difference in sucrose preference were randomly separated into four groups (n = 12): sham-operated group; perimenopausal depression model group; model + 50 mg/kg.bw quercetin group; model + 0.27 mg/kg.bw 17β-estradiol group. After successful modeling, adrenal gland and hypothalamic samples were collected for metabolomics experiments and detection of related indicators. A total of 22 differential metabolites were identified in the model group, and pathway analysis revealed adrenal gland metabolism abnormalities including steroid hormone biosynthesis, arachidonic acid metabolism, and linoleic acid metabolism. Notably, Spearman's rank correlation analysis between differential metabolites and rat behavioral results showed strong positive or negative correlations (P < 0.01). Meanwhile, the hypothalamus of the model group showed TrkB-BDNF signaling pathway abnormality, and the HPA axis was found to play an important role in perimenopausal depression. Treatment with quercetin or 17β-estradiol restored these abnormal changes. It suggested that quercetin can regulate adrenal metabolic disorders through multiple pathways, thereby ameliorating perimenopausal depression.Further more, quercetin can modulate HPA axis through the TrkB-BDNF signaling pathway. This research provides new ideas for the application of quercetin in the precaution and treatment of perimenopausal depression.

Sterols and bile acids are vital signaling molecules that play key roles in systemic functions, influencing the composition of the human gut microbiota, which maintains a symbiotic relationship with the host. Additionally, gut microbiota-encoded enzymes catalyze the conversion of sterols and bile acids into various metabolites, significantly enhancing their diversity and biological activities. In this review, we focus on the microbial transformations of sterols and bile acids in the gut, summarize the relevant bacteria, genes, and enzymes, and review the relationship between the sterols and bile acids metabolism of gut microbiota and human health. This review contributes to a deeper understanding of the crucial roles of sterols and bile acids metabolism by gut microbiota in human health, offering insights for further investigation into the interactions between gut microbiota and the host.

While increasing evidence suggests that alterations in the gut microbiota and metabolites are associated with ovarian cancer (OC) risk, whether these associations imply causation remains to be identified.

We conducted a two-sample Mendelian randomization (MR) study utilizing a large-scale genome-wide association study (GWAS) to explore the causal effects of the gut microbiota of 196/220 individuals and 1,400 plasma metabolites on OC and epithelial ovarian cancer (EOC) subtypes. Data on the gut microbiota were obtained from the MiBioGen consortium of 18,340 subjects and the Dutch Microbiome Project of 7,738 volunteers. Data on plasma metabolites were derived from a GWAS of plasma metabolites in 8,299 participants. Ovarian cancer (n = 25,509) and EOC subtypes were obtained from the Ovarian Cancer Association Consortium (OCAC). Metabolites and associated targets were analyzed via network pharmacology and molecular docking.

At the genus and species levels, we identified seven risk factors for the gut microbiota: the genus Dialister (P = 0.024), genus Ruminiclostridium5 (P = 0.0004), genus Phascolarctobacterium (P = 0.0217), species Bacteroides massiliensis (P = 0.011), species Phascolarctobacterium succinatutens (P = 0.0212), species Paraprevotella clara (P = 0.0247) and species Bacteroides dorei (P = 0.0054). In addition, five gut microbes at the genus and species levels were found to be protective: genus Family XIII AD3011 group (P = 0.006), genus Butyrivibrio (P = 0.0095), genus Oscillibacter (P = 0.0206), species Roseburia hominis (P = 0.0241), and species Bifidobacterium bifidum (P = 0.0224). For plasma metabolites, we revealed five positive and four negative correlations with OC. Among these, caffeic acid and caffeine metabolites and sphingomyelin and ceramide metabolites were identified as risk factors, whereas phenylalanine metabolites, butyric acid metabolites, and some lipid metabolites were recognized as protective factors. A series of sensitivity analyses revealed no abnormalities, including pleiotropy and heterogeneity analyses.

Our MR analysis demonstrated that the gut microbiota and metabolites are causally associated with OC, which has significant potential for the early detection and diagnosis of OC and EOC subtypes, providing valuable insights into this area of research.

The sex difference in depression has long been an unsolved issue. Women are twice as likely to suffer from depression as men. However, there were significant differences in the composition of gut microbiota between women and men. There is a lack of studies linking sex differences in depression to microbiota, and the specific mechanisms of this process have not been explained in detail. The main purpose of this study was to explore the gender differences in the intestinal tract of male and female depressed mice. In this study, chronic restraint stress (CRS) mouse models were used to simulate chronic stress, and behavioral tests were conducted, including the open field test (OFT), tail suspension test (TST) and forced swimming test (FST). Microbial diversity analysis and metabolomics were performed on collected mouse feces. The results showed that female mice were highly active and prone to anxious behavior before stress, and the levels of f-Rikenellaceae, f-Ruminococcaceae and 16α-hydroxyestrone were significantly different from those in male mice. After 21 days (Days) of stress, female mice showed depression-like behavior, and the levels of f-Erysipelotrichaceae, 5α-pregnane-3,20-dione, and 2-hydroxyestradiol were significantly different from those in male mice. After 14 days of stress withdrawal, the depression-like behavior continued to worsen in female mice, and the levels of 5α-pregnane-3,20-dione, estrone glucuronide and f-Erysipelotrichaceae were significantly different from those in male mice. In summary, female mice have stronger stress sensitivity and weaker resilience than male mice, which may be related to differences in bacterial diversity and estrogen metabolism disorders.

Pain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic-pituitary-adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated. EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with Bacteroides, while aspartate uptake in the spinal cord positively correlated with the relative abundance of Lachnospiraceae NK4A136. Positive associations with aspartate uptake in the spinal cord were also observed for Alistipes and Bifidobacterium during oestrus, and Eubacterium coprostanoligenes during proestrus. Clostridium sensu stricto1 was negatively associated with aspartate uptake in the ACC in males and dioestrus females. These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.

The recurrence and treatment resistance of depression remain significant issues, primarily due to an inadequate understanding of its pathogenesis. Recent scientific evidence indicates that gut microbiota influence estradiol metabolism and are associated with the development of depression in nonpremenopausal women. Integrating existing studies on the regulation of estradiol metabolism by microorganisms in nature and the relevance of its degradation products to depression, recent scientific explorations have further elucidated the key mechanisms by which gut microbiota catabolize estradiol through specific metabolic pathways. These emerging scientific findings suggest that the unique metabolic effects of gut microbiota on estradiol may be one of the central drivers in the onset and course of depression in non-menopausal women.

The gut microbiota is a highly complex microbial community residing in the digestive tract of humans and animals, closely linked to host health. Dysbiosis within the gut microbiota has been associated with various diseases. Moreover, it interacts with the female reproductive system's microbiota, influencing maternal reproductive homeostasis. Although the gut microbiota holds potential for treating reproductive system diseases and modulating offspring fertility, research in this domain remains limited. This review examines the relationship between both balanced and imbalanced gut microbiota and reproductive system diseases, as well as their effects on fetal development. It is highlighted that dysbiosis in the gut microbiota may contribute to several reproductive conditions, including polycystic ovary syndrome (PCOS), preeclampsia (PE), endometriosis, gestational diabetes, and reproductive cancers. The abundance of specific gut microbial species or interactions among various species can influence the reproductive system through hormonal pathways and other mechanisms, ultimately affecting pregnancy outcomes and fetal health. Therefore, the concept of the gut-reproductive axis is proposed, emphasizing the significant role of maternal gut microbiota in shaping fetal development, metabolic capacity, and immunity.

Evidence suggests that complex interactions among the gut microbiome, metabolic abnormalities, and brain have important etiological and therapeutic implications in major depressive disorder (MDD). However, the influence of microbiome-gut-brain cross-talk on cognitive impairment in MDD remains poorly characterized. We performed serum metabolomic profiling on 104 patients with MDD and 77 healthy controls (HCs), and also performed fecal metagenomic sequencing on a subset of these individuals, including 79 MDD patients and 60 HCs. The findings were validated in a separate cohort that included 40 patients with MDD and 40 HCs using serum-targeted metabolomics. Abnormal bile acid metabolism was observed in patients with MDD, which is related to cognitive dysfunction. The following gut microbiota corresponded to changes in bile acid metabolism and enzyme activities involved in the bile acid metabolic pathway, including Lachnospiraceae (Blautia_massiliensis, Anaerostipes_hadrus, Dorea_formicigenerans, and Fusicatenibacter_saccharivorans), Ruminococcaceae (Ruminococcus_bromii, Flavonifractor_plautii, and Ruthenibacterium_lactatiformans), and Escherichia_coli. Furthermore, a combinatorial marker classifier that robustly differentiated patients with MDD from HCs was identified. In conclusion, this study provides insights into the gut-brain interactions in the cognitive phenotype of MDD, indicating a potential therapeutic strategy for MDD-associated cognitive impairment by targeting the gut microbiota and bile acid metabolism.

Sex differences in the gut microbiome have been examined previously, but results are inconsistent, often due to small sample sizes. We investigated sex and menopausal differences in the gut microbiome in a large multi-ethnic population cohort study, including 5166 participants. Using machine learning models, we revealed modest associations between sex and menopausal status, and gut microbiota composition (AUC 0.61-0.63). After adjustments for age, cardiovascular risk factors, and diet, a part of the associations of the highest-ranked gut microbes with sex were attenuated, but most associations remained significant. In contrast, most associations with menopausal status were driven by age and lost significance after adjustment. Using pathway analyses on metagenomic data, we identified sex differences in vitamin B6 synthesis and stachyose degradation pathways. Since some of sex differences in gut microbiome composition and function could not be explained by covariates, we recommend sex stratification in future microbiome studies.

The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy. Key findings include the microbiome's role in bone metabolism through hormone regulation and production of short-chain fatty acids, crucial for mineral absorption. The review also considers the effects of diet, probiotics, and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health. While promising, challenges in translating microbiome research into clinical practice persist, necessitating further exploration and ethical consideration of microbiome-based therapies. This interdisciplinary research aims to link digestive health with musculoskeletal integrity, offering new insights into the prevention and management of bone and joint diseases.

Neurological diseases are the primary cause of disability and death and impose substantial financial burdens. However, existing treatments only relieve symptoms and may cause many adverse effects. Natural products are a promising source of neurological therapeutic agents due to their excellent neuroprotective effect and safety. The gut microbiota has an essential impact on maintaining brain homeostasis via the gut-brain axis. Multiple investigations show that natural products offer neuroprotective effects by regulating gut microbiota-driven signaling networks.

This review aims to provide a systematic review of how natural products promote neurological health by harnessing the power of gut microbiota.

The pre-January 1, 2024 literature was gathered from several databases, including Scopus, PubMed, Google Scholar, and Web of Science, utilizing appropriate keywords. The gathered publications underwent a review process and were classified based on their study content, specifically focusing on the impact of natural products on gut microbiota and neurological health.

Here, we review how natural products promote neurological health by regulating the gut microbiota-brain axis. Specifically, we focus on the following areas. (1) Altering microorganism community structure, including increasing α-diversity and altering β-diversity. (2) Regulating the population of certain bacteria, including enriching beneficial microorganisms Akkermansia and Bifidobacterium, and inhibiting potentially hazardous microorganisms Bilophila, Klebsiella, and Helicobacter. (3) Regulating microbial neuroactive metabolites levels, including short-chain fatty acids, tryptophan and its derivatives, trimethylamine N-oxide, dopa/dopamine, γ-aminobutyric acid, and lipopolysaccharide. Furthermore, we review how natural products promote neurological health by regulating intestinal barrier homeostasis.

Natural products promote neurological health by harnessing the power of gut microbiota. This review will contribute to understanding how natural products promote neurological health by orchestrating the gut microbiota-brain axis.

Testosterone deficiency can cause abnormal lipid metabolism in men, leading to hyperlipidemia. We identified the testosterone-degrading bacterium Pseudomonas nitroreducens in the fecal samples of male patients with hyperlipidemia. Gastric administration of P. nitroreducens in mice led to testosterone deficiency and elevated blood lipid levels. Whole-genome sequencing of P. nitroreducens revealed the presence of 3/17β-hydroxysteroid dehydrogenase (3/17β-HSD), a gene responsible for testosterone degradation, which is also associated with hyperlipidemia. Microbiota analysis of fecal samples collected from 158 patients with hyperlipidemia and 151 controls revealed that the relative abundance of P. nitroreducens and 3/17β-HSD in the fecal samples of patients with hyperlipidemia was significantly higher than that in controls. These results suggest that P. nitroreducens and 3/17β-HSD may be related to the onset of testosterone deficiency-induced hyperlipidemia. Therefore, treatments targeted at eradicating testosterone-degrading bacteria are a potential future option for patients with testosterone-induced hyperlipidemia and should thus be studied further.

Patients with Alzheimer's disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut-brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production.

The gut microbiome plays pivotal roles in various physiological and pathological processes, with key metabolites including short chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (TRP) derivatives gaining significant attention for their diverse physiological roles. However, quantifying these metabolites presents challenges due to structural similarity, low abundance, and inherent technical limitations in traditional detection methods. In this study, we developed a precise and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing a chemical isotope derivatization technique employing 4-(aminomethyl)-N,N-dimethylaniline-d0/d6 (4-AND-d0/d6) reagents to quantify 37 typical gut microbiome-derived metabolites. This method achieved an impressive 1500-fold enhancement in sensitivity for detecting metabolites, compared to methods using non-derivatized, intact molecules. Moreover, the quantitative accuracy of our chemical isotope derivatization strategy proved comparable to the stable isotope labeled internal standards (SIL-IS) method. Subsequently, we successfully applied this newly developed method to quantify target metabolites in plasma, brain, and fecal samples obtained from a neonatal hypoxic-ischemic encephalopathy (HIE) rat model. The aim was to identify crucial metabolites associated with the progression of HIE. Overall, our sensitive and reliable quantification method holds promise in elucidating the role of gut microbiome metabolites in the pathogenesis of various diseases.

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity.

Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

The functioning of the brain and its impact on behavior, emotions, and cognition can be affected by both neurological and psychiatric disorders that impose a significant burden on global health. Phytochemicals are helpful in the treatment of several neurological and psychological disorders, including anxiety, depression, Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD), because they have symptomatic benefits with few adverse reactions. Changes in gut microbiota have been associated with many neurological and psychiatric conditions. This review focuses on the potential efficacy of phytochemicals such as flavonoids, terpenoids, and polyphenols in regulating gut flora and providing symptomatic relief for a range of neurological and psychological conditions. Evidence-based research has shown the medicinal potentials of these phytochemicals, but additional study is required to determine whether altering gut microbiota might slow the advancement of neurological and psychological problems.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like β-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Microplastics (MPs) existing extensively in various ecosystems can be ingested by marine organisms and enter the food chain, resulting the health risks from the presence of MPs in aquatic and terrestrial ecosystems. In the present study, an ideal model for Lepidoptera, the silkworm, Bombyx mori, was exposed to environmental concentrations (0.125 μg, 0.25 μg or 0.5 μg/diet) of MPs for 5 days, and the global changes in gut microbes and metabolites were subsequently examined via 16S rDNA sequencing and GC‒MS-based metabolomics. The results showed that MPs exposure did not seriously threaten survival but may regulate signaling pathways involved in development and cocoon production. MPs exposure induced gut microbiota perturbation according to the indices of α-diversity and β-diversity, and the functional prediction of the altered microbiome and associated metabolites demonstrated the potential roles of the altered microbiome following MPs exposure in the metabolic and physiological states of silkworm. The metabolites markedly altered following MPs exposure may play vital biological roles in energy metabolism, lipid metabolism, xenobiotic detoxification and the immune system by directly or indirectly affecting the physiological state of silkworms. These findings contribute to assessing the health risks of MPs exposure in model insects and provide novel insight into the toxicity mechanism of MPs.

Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear.

The objective of this work is to examine the alteration of gut microbiota in patients with CS.

We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS.

We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro.

This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.

Depression represents a prevalent and enduring mental disorder of significant concern within the clinical domain. Extensive research indicates that depression is very complex, with many interconnected pathways involved. Most research related to depression focuses on monoamines, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, tryptophan metabolism, energy metabolism, mitochondrial function, the gut-brain axis, glial cell-mediated inflammation, myelination, homeostasis, and brain neural networks. However, recently, Ketamine, an ionotropic N-methyl-D-aspartate (NMDA) receptor antagonist, has been discovered to have rapid antidepressant effects in patients, leading to novel and successful treatment approaches for mood disorders. This review aims to summarize the latest findings and insights into various signaling pathways and systems observed in depression patients and animal models, providing a more comprehensive view of the neurobiology of anxious-depressive-like behavior. Specifically, it highlights the key mechanisms of ketamine as a rapid-acting antidepressant, aiming to enhance the treatment of neuropsychiatric disorders. Moreover, we discuss the potential of ketamine as a prophylactic or therapeutic intervention for stress-related psychiatric disorders.

Catalytic activity is undoubtedly a key focus in enzyme engineering. The complicated reaction conditions hinder some enzymes from industrialization even though they have relatively promising activity. This has occurred to some dehydrogenases. Hydroxysteroid dehydrogenases (HSDHs) specifically catalyze the conversion between hydroxyl and keto groups, and hold immense potential in the synthesis of steroid medicines. We underscored the importance of 7α-HSDH activity, and analyzed the overall robustness and underlying mechanisms. Employing a high-throughput screening approach, we comprehensively assessed a mutation library, and obtained a mutant with enhanced enzymatic activity and overall stability/tolerance. The superior mutant (I201M) was identified to harbor improved thermal stability, substrate susceptibility, cofactor affinity, as well as the yield. This mutant displayed a 1.88-fold increase in enzymatic activity, a 1.37-fold improvement in substrate tolerance, and a 1.45-fold increase in thermal stability when compared with the wild type (WT) enzyme. The I201M mutant showed a 2.25-fold increase in the kcat/KM ratio (indicative of a stronger binding affinity for the cofactor). This mutant did not exhibit the highest enzyme activity compared with all the tested mutants, but these improved characteristics contributed synergistically to the highest yield. When a substrate at 100 mM was present, the 24 h yield by I201M reached 89.7%, significantly higher than the 61.2% yield elicited by the WT enzyme. This is the first report revealing enhancement of the catalytic efficiency, cofactor affinity, substrate tolerance, and thermal stability of NAD(H)-dependent 7α-HSDH through a single-point mutation. The mutated enzyme reached the highest enzymatic activity of 7α-HSDH ever reported. High enzymatic activity is undoubtedly crucial for enabling the industrialization of an enzyme. Our findings demonstrated that, when compared with other mutants boasting even higher enzymatic activity, mutants with excellent overall robustness were superior for industrial applications. This principle was exemplified by highly active enzymes such as 7α-HSDH.

The escalating prescription of psychopharmacological medications to women of reproductive age underscores the growing significance of sex-specific variations in pharmacotherapy. Despite this, clinical trials have largely overlooked these differences. Preliminary data indicate sex-specific variations in the neurobiology of affective disorders and in the metabolism, pharmacodynamics, and kinetics of therapeutic drugs. This underscores the imperative for a more nuanced exploration of menstrual cycle-dependent fluctuations in psychotropic drugs. This pilot study aimed to investigate drug and hormone fluctuations in female patients with affective disorders, aiming to enhance comprehension of the interplay between cycle-related hormone fluctuations and pharmacokinetics. The ultimate goal is to facilitate more effective and safer pharmacological therapy in the future.

Blood samples were collected from 27 patients and 27 age-matched control participants at 3 distinct time points (early follicular phase, ovulation, and late luteal phase) during each menstrual cycle. Depressive and manic symptoms were assessed, and hormone concentrations were measured in the entire sample, while drug concentrations were assessed solely in the affective disorder sample using mass spectrometry.

Significant variations in drug concentration were observed throughout the menstrual cycle for bupropion, with a trend toward altered concentration for venlafaxine. Moreover, notable differences in hormone concentrations were identified between patients and controls, even after accounting for the impact of contraceptive use, diagnoses, and medication.

This pilot study reinforces previously reported data, underscoring the significance of sex-specific pharmacological therapy approaches. It provides further evidence supporting the interaction among sex hormones, drugs, and symptoms of affective disorders.

Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.

The complex, bidirectional interactions between the brain, the gut, and the gut microbes are best referred to as the brain gut microbiome system. Animal and clinical studies have identified specific signaling mechanisms within this system, with gut microbes communicating to the brain through neuronal, endocrine, and immune pathways. The brain, in turn, modulates the composition and function of the gut microbiota through the autonomic nervous system, regulating gut motility, secretion, permeability, and the release of hormones impacting microbial gene expression. Perturbations at any level of these interactions can disrupt the intricate balance, potentially contributing to the pathogenesis of intestinal, metabolic, neurologic, and psychiatric disorders. Understanding these interactions and their underlying mechanisms holds promise for identifying biomarkers, as well as novel therapeutic targets, and for developing more effective treatment strategies for these complex disorders. Continued research will advance our knowledge of this system, with the potential for improved understanding and management of a wide range of disorders. This review provides an update on the current state of knowledge regarding this system, with a focus on recent advancements and emerging research areas.

The aim of this quasi-experimental study was to determine the alterations in gut microbiota and metabolism in humans who consume hot food served in disposable plastic tableware (DPT). Participants in the exposure and control groups were provided three hot meals in DPT (n = 30) or non-DPT (n = 30), respectively. After a month of observation, individuals in the exposure group discontinued the three meals provided in DPT (n = 27) for 1 month as the post-exposure group. Fecal samples were collected and tested for microplastics (MPs) detection using LDIR and gut microbiota identification based on the 16 S rRNA. Urine samples were used for metabolite analysis using LC-MS/MS. Results showed that the level of MPs in feces was lower in the post-exposure group compared with the exposure group. Furthermore, the abundance of the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidota in the exposure and post-exposure groups were significantly different compared with the control group. Changes in microbiota abundance and metabolite levels were mainly associated with central nervous system effects, energy metabolism, and inflammation, suggesting that thermal exposure to DPT for 1 month has considerable health effects.

Recent work on bile salt hydrolases (BSHs) in Gram-negative bacteria, such as Bacteroides, has primarily focused on how they can impact host physiology. However, the benefits bile acid metabolism confers to the bacterium that performs it are not well understood. In this study, we set out to define if and how Bacteroides thetaiotaomicron (B. theta) uses its BSHs and hydroxysteroid dehydrogenase to modify bile acids to provide a fitness advantage for itself in vitro and in vivo. Genes encoding bile acid-altering enzymes were able to impact how B. theta responds to nutrient limitation in the presence of bile acids, specifically carbohydrate metabolism, affecting many polysaccharide utilization loci. This suggests that B. theta may be able to shift its metabolism, specifically its ability to target different complex glycans including host mucin, when it comes into contact with specific bile acids in the gut.

Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.