Parkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the "gut-brain axis." Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.

Gut microbiota play a critical role in mediating the bidirectional association between cancer and depression. Emerging evidence indicates that adjusting the dietary component intake can significantly alter gut microbiota composition, thereby influencing the host's metabolism and immune function. Changes in gut microbiota and their metabolites may represent key factors in preventing cancer-depression comorbidity.

English publications were searched in databases including the Web of Science, Scopus, and PubMed using a series of keywords: "cancer", "depression", "gut microbiota", "dietary components", and related terms, individually or in combination. The search focused on preclinical and clinical studies describing the regulatory effects of dietary component interventions.

This narrative review summarizes the associations among gut microbiota, cancer, and depression, and synthesizes current evidence on the modulatory effects and mechanisms of specific dietary component interventions, including dietary patterns, probiotics, prebiotics, and diet-derived phytochemicals, on gut microbiota. On the one hand, these interventions inhibit abnormal proliferation signals in the tumor microenvironment and enhance anticancer immune responses; on the other hand, they modulate neurotransmitter homeostasis, suppress neuroinflammation, and improve mood behaviors through the gut-brain axis interactions mediated by microbial metabolites.

The complex associations among cancer, depression, and gut microbiota require further clarification. Modulating gut microbiota composition through dietary components represents a novel therapeutic strategy for improving cancer-depression comorbidity. Regulated gut microbiota enhance immune homeostasis and intestinal barrier function, while their metabolites bidirectionally modulate one another via systemic circulation and the gut-brain axis, thereby improving both the tumor microenvironment and depressive-like behaviors in cancer patients while reducing the adverse effects of cancer.

One of the major issues modern medicine faces is the increasing use of antibiotics in reaction to the increased incidence of infectious agents. The current trend of antibiotic overuse contributes to microbial dysbiosis. Recent studies have hypothesized that antibiotic exposure during pregnancy, which alters the composition of the microbiome, might increase the likelihood of attention deficit hyperactivity disorder (ADHD). In addition to the ongoing discussion about the potential links between antibiotic usage, microbiome dysbiosis, and ADHD, there is a rising interest in integrating AI and ML into healthcare practices. Diagnosis, treatment plans, and prognoses are all enhanced by these technological advancements. Remote monitors or telemedicine monitoring are among the management techniques described in this chapter for effectively managing illnesses. Also discussed are ways to halt the progression of diseases by preventative measures that use biosensor technology and dietary approaches. Personalized treatment programs, disease progression stages, and prognosis evaluations are all made possible with the use of artificial intelligence and machine learning. By using these technologies to provide individualized therapy, healthcare practitioners may get a better understanding of ADHD and perhaps improve patient outcomes.

Ageing is a scientifically fascinating and complex biological occurrence characterised by morphological and functional changes due to accumulated molecular and cellular damage impairing tissue and organ function. Ageing is often accompanied by cognitive decline but is also the biggest known risk factor for Alzheimer's disease, the most common form of dementia. Emerging evidence suggests that sedentary and unhealthy lifestyles accelerate brain ageing, while regular physical activity, high cardiorespiratory fitness (CRF), or a combination of both, can mitigate cognitive impairment and reduce dementia risk. The purpose of this Review is to explore the neuroprotective mechanisms of endurance exercise and highlight the importance of CRF in promoting healthy brain ageing. Key findings show how CRF mediates the neuroprotective effects of exercise via mechanisms such as improved cerebral blood flow, reduced inflammation, and enhanced neuroplasticity. We summarise evidence supporting the integration of endurance exercise that enhances CRF into public health initiatives as a preventive measure against age-related cognitive decline. Additionally, we address important challenges such as lack of long-term studies with harmonised study designs across preclinical and clinical settings, employing carefully controlled and repeatable exercise protocols, and outline directions for future research.

Music intervention is gaining recognition as a cost-effective therapeutic for improving human health. Despite its growing application, the mechanisms through which music exerts beneficial health effects remain largely unexplored. Here, we show that music can exert beneficial effects in mice through modulating gut microbiome composition. Adult mice were exposed to ambient noise, Mozart's Flute Quartet in D Major, K. 285, or white noise over a three-week period. Afterward, we observed treatment-specific changes in the community of gut commensal bacteria in these animals. Upon subsequent challenge with the bacterial pathogen Salmonella typhimurium, control groups exhibited significant weight loss and increased Salmonella colonization, whereas the Mozart-treated group did not. 16S ribosomal RNA gene sequencing revealed that the Mozart group showed a significant increase in Lactobacillus salivarius, a probiotic known for its antibacterial properties. Further experiments confirmed that L. salivarius mitigated Salmonella infection in mice and that L. salivarius acidified local environments in in vitro culture, thus inhibiting Salmonella growth. Additionally, mice exposed to Mozart consumed more food but showed similar body weight compared to the control groups. Behavioral assessments, including open field and object location tests, revealed that Mozart-treated mice were more active, less anxious, and exhibited enhanced spatial memory. Finally, Mozart exposure was shown to significantly boost colonization of administered L. salivarius and alter gut metabolite profiles. These findings suggest that music exposure fosters healthier gut microbiota, enhancing resistance to bacterial infections and highlighting the potential of music therapy as a novel strategy to combat drug-resistant pathogen infections.

Music therapy is increasingly recognized as a low-cost approach to improving health, but how it works remains unclear. Our study demonstrates that music can positively influence health by altering the gut microbiome. In a mouse model, exposure to Mozart's Flute Quartet in D Major enhanced the gut microbiota, specifically increasing levels of the beneficial bacterium Lactobacillus salivarius. This probiotic protected mice from Salmonella infection by creating an acidic environment that inhibited pathogen growth. Mozart-treated mice also showed reduced anxiety, better spatial memory, and higher food intake without weight gain, suggesting the benefits of music exposure. These findings reveal a novel link between music, gut health, and disease resistance, suggesting that music therapy could be a promising strategy for enhancing gut microbiota and combating infections, including those caused by drug-resistant bacteria.

There is mounting evidence for the involvement of the immune system, neuroinflammation and disturbed gut microbiota, or dysbiosis, in attention-deficit/hyperactivity disorder (ADHD). Gut dysbiosis is strongly implicated in many physical, autoimmune, neurological, and neuropsychiatric conditions, however knowledge of its particular pathogenic role in ADHD is sparse. As such, this narrative review examines and synthesizes the available evidence related to inflammation, dysbiosis, and neural processes in ADHD. Minimal differences in microbiota diversity measures between cases and controls were found, however many relative abundance differences were observed at all classification levels (phylum to strain). Compositional differences of taxa important to key gut-brain axis pathways, in particular Bacteroides species and Faecalibacterium, may contribute to inflammation, brain functioning differences, and symptoms, in ADHD. We have identified one possible model of ADHD etiopathogenesis involving systemic inflammation, an impaired blood-brain barrier, and neural disturbances as downstream consequences of gut dysbiosis. Nevertheless, studies conducted to date have varied degrees of methodological rigour and involve diverse participant characteristics and analytical techniques, highlighting a need for additional research.

Intestinal crypts harbour a specific microbiota but whether and how these bacteria regulate intestinal stem cells (ISCs) or influence colorectal cancer (CRC) development is unclear. Here we screened crypt-resident bacteria in organoids and found that indole acetic acid (IAA) secreted by Acinetobacter radioresistens inhibits ISC turnover. A. radioresistens inhibited cellular proliferation in tumour slices from CRC patients and inhibited intestinal tumorigenesis and spheroid initiation in APCMin/+ mice. Targeted clearance of A. radioresistens from colonic crypts using bacteriophage increased EphB2 expression and consequently promoted cellular proliferation, ISC turnover and tumorigenesis in mouse models of CRC. The protective effects of A. radioresistens were abrogated upon deletion of trpC to prevent IAA production, or upon intestine-specific aryl hydrocarbon receptor (AhR) knockout, identifying an IAA-AhR-Wnt-β-catenin signalling axis that promotes ISC homeostasis. Our findings reveal a protective role for an intestinal crypt-resident microbiota member in tumorigenesis.

Aging is associated with alternative splicing (AS) defects that have broad implications on aging-associated disorders. However, which drug(s) can rescue age-related AS defects and extend lifespan has not been systematically explored. We performed large-scale compound screening in C. elegans using a dual-fluorescent splicing reporter system. Among the top hits, doxifluridine, a fluoropyrimidine derivative, rescues age-associated AS defects and extends lifespan. Combining bacterial DNA sequencing, proteomics, metabolomics and the three-way screen system, we further revealed that bacterial ribonucleotide metabolism plays an essential role in doxifluridine conversion and efficacy. Furthermore, doxifluridine increases production of bacterial metabolites, such as linoleic acid and agmatine, to prolong host lifespan. Together, our results identify doxifluridine as a potent lead compound for rescuing aging-associated AS defects and extending lifespan, and elucidate drug's functions through complex interplay among drug, bacteria and host.

Irritable bowel syndrome (IBS) is a multifactorial disorder of the gut-brain axis, characterized by visceral hypersensitivity (VH). Psychobiotics, through GABA synthesis, are good candidates to alleviate gastrointestinal discomfort. Here, we analyzed the GABA-producer Lactococcus lactis CNCM I-5388 as an active-enzyme postbiotic to relieve VH mediated by psychological stress. L. lactis CNCM I-5388 was inactivated by ethanol while maintaining its glutamate decarboxylase (GAD) activity. This EtOH-treated nonviable form was given daily orally for 1, 5, or 10 days to female Wistar rats in comparison with viable L. lactis CNCM I-5388 or vehicle. Visceral sensitivity was measured by electromyography before and after partial restraint stress (PRS). GABA was quantified in the stomach collected from rats and in the gastric compartment of TIM-1 human gut model in fed state. A daily treatment for 5 and 10 days by L. lactis CNCM I-5388 both in its viable and nonviable forms counteracted VH promoted by PRS. However, only viable L. lactis CNCM I-5388 tended to reduce VH after a single administration. After 5-day treatment, only under PRS conditions, the production of GABA within the stomach was enhanced in rats treated with viable or nonviable L. lactis CNCM I-5388. This increase was confirmed by using the TIM-1 human gut model. We found that a postbiotic with an active-GAD enzyme of L. lactis CNCM I-5388, similarly to its viable psychobiotic form, exerts anti-VH properties in an IBS-like rat model. These effects are associated with GABA production in the stomach where the low pH promotes GAD activity.

Adult neural stem cells divide to produce neurons that migrate to preexisting neuronal circuits in a process named adult neurogenesis. Adult neurogenesis is one of the most exciting areas of current neuroscience, and it may be involved in a range of brain functions, including cognition, learning, memory, and social and behavior changes. While there is a growing number of multi-omics studies on adult neurogenesis, generalized analyses from a multi-omics perspective are lacking. In this review, we summarize studies related to genomics, metabolomics, proteomics, epigenomics, transcriptomics, and microbiomics of adult neurogenesis, and then discuss their future research priorities and potential neighborhoods. This will provide theoretical guidance and new directions for future research on adult neurogenesis.

The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients' offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings' stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings' stem cells and represent a promising target for interventions.

A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell-cell interactions during specific age. Different T cell subsets displayed different aging patterns in both transcriptomes and immune repertoires; examples included GNLY+CD8+ effector memory T cells, which exhibited the highest clonal expansion among all T cell subsets and displayed distinct functional signatures in children and the elderly; and CD8+ MAIT cells, which reached their peaks of relative abundance, clonal diversity and antibacterial capability in adolescents and then gradually tapered off. Interestingly, we identified and experimentally verified a previously unrecognized 'cytotoxic' B cell subset that was enriched in children. Finally, an immune age prediction model was developed based on lifecycle-wide single-cell data that can evaluate the immune status of healthy individuals and identify those with disturbed immune functions. Our work provides both valuable insights and resources for further understanding the aging of the immune system across the whole human lifespan.

Changes in gut microbiota composition have been linked to anxiety behavior in rodents. However, the underlying neural circuitry linking microbiota and their metabolites to anxiety behavior remains unknown. Using male C57BL/6J germ-free (GF) mice, not exposed to live microbes, increased anxiety-related behavior was observed correlating with a significant increase in the immediate early c-Fos gene in the basolateral amygdala (BLA). This phenomenon coincided with increased intrinsic excitability and spontaneous synaptic activity of BLA pyramidal neurons associated with reduced small conductance calcium-activated potassium (SK) channel currents. Importantly, colonizing GF mice to live microbes or the microbial-derived metabolite indoles reverted SK channel activities in BLA pyramidal neurons and reduced the anxiety behavioral phenotype. These results are consistent with a molecular mechanism by which microbes and or microbial-derived indoles, regulate functional changes in the BLA neurons. Moreover, this microbe metabolite regulation of anxiety links these results to ancient evolutionarily conserved defense mechanisms associated with anxiety-related behaviors in mammals.

The mammalian nervous system is impacted by aging. Aging alters brain architecture, is associated with molecular damage, and can manifest with cognitive and motor deficits that diminish the quality of life. Astrocytes are glial cells of the CNS that regulate the development, function, and repair of neural circuits during development and adulthood; however, their functions in aging are less understood. Astrocytes change their transcriptome during aging, with astrocytes in areas such as the cerebellum, the hypothalamus, and white matter-rich regions being the most affected. While numerous studies describe astrocyte transcriptional changes in aging, many questions still remain. For example, how is astrocyte function altered by transcriptional changes that occur during aging? What are the mechanisms promoting astrocyte aged states? How do aged astrocytes impact brain function? This review discusses features of aged astrocytes and their potential triggers and proposes ways in which they may impact brain function and health span.

The intestinal microbiota plays a fundamental role in maintaining host health, especially during childhood, a critical period for its establishment. Early life stress can lead to shifts in gut microbiota composition, thus increasing the risk of major depressive disorder (MDD) in adulthood. The supplementation with probiotics restores intestinal permeability and the health of gut microbial communities, therefore being potential study targets for the treatment of MDD. In this sense, the yeast Komagataella pastoris was reported as a promising probiotic with antidepressant effect.

Hence, the present study aims to investigate this effect in mice submitted to maternal separation (MS) 3 h per day from PND2 to PND14. Adult mice and mothers were treated with K. pastoris KM71H (8 log UFC.g-1/per animal, i.g.) or PBS (500 µl, i.g.) for 14 days. After behavioral tests, the animals were euthanized, followed by hippocampi and intestines removal for biochemical analysis.

On behavioral tests, K. pastoris KM71H treatment reduced the immobility time in TST of adult mice and increased the grooming activity in splash test of adult mice and mothers induced by MS. The probiotic treatment restored plasma corticosterone levels and glucocorticoid receptor expression in hippocampi, alongside nitrate/nitrite levels and superoxide dismutase activity in intestine, in addition to reducing reactive species levels in both structures. Moreover, it also normalized the fecal pH and water content of feces.

Thus, we conclude that K. pastoris KM71H is a promising therapeutic strategy for the treatment of MDD.

Stunting become a global concern because it's not only affecting physical stature, but also affecting on neurodevelopment and cognitive function. These impacts are resulting in long-term consequences especially for human resources, such as poor-quality labor, decreased productivity due to decreasing of health quality, including immunity and cognitive aspect.

This comprehensive review found that based on many studies, there is an altered gut microbiota, or dysbiosis, in stunted children, causing the impairment of brain development through Microbiota-Gut Brain Axis (MGB Axis) mechanism. The administration of probiotics has been known affect MGBA by improving the physical and chemical gut barrier integrity, producing antimicrobial substance to inhibit pathogen, and recovering the healthy gut microbiota. Probiotics, along with healthy gut microbiota, produce SCFAs which have various positive impact on CNS, such as increase neurogenesis, support the development and function of microglia, reduce inflammatory signaling, improve the Blood Brain Barrier's (BBB's) integrity, produce neurotropic factors (e.g. BDNF, GDNF), and promote the formation of new synapse. Probiotics also could induce the production of IGF-1 by intestinal epithelial cells, which functioned as growth factor of multiple body tissues and resulted in improvement of linear growth as well as brain development.

These properties of probiotics made it become the promising and feasible new treatment approach for stunting. But since most of the studies in this field are conducted in animal models, it is necessary to translate animal data into human models and do additional study to identify the numerous components in the MGB axis and the effect of probiotics on human.

Recent evidence challenging the notion of a sterile intrauterine environment has sparked research into the origins and effects of fetal microbiota on immunity development during gestation. Rhesus macaques (RMs) serve as valuable nonhuman primate models due to their similarities to humans in development, placental structure, and immune response. In this study, metagenomic analysis was applied to the placenta, umbilical cord, spleen, gastrointestinal tissues of an unborn RM fetus, and the maternal intestine, revealing the diversity and functionality of microbes in these tissues. Additionally, gut metagenomic data of adult Rhesus macaques from our previous study, along with data from a human fetus obtained from public databases, were included for comparison. We observed substantial microbial sharing between the mother and fetus, with the microbial composition of the placenta and umbilical cord more closely resembling that of the fetal organs than the maternal intestine. Notably, compared with other adult RMs, there was a clear convergence between maternal and fetal microbiota, alongside distinct differences between the microbiota of adults and the fetus, which underscores the unique microbial profiles in fetal environments. Furthermore, the fetal microbiota displayed a less developed carbohydrate metabolism capacity than adult RMs. It also shared antibiotic resistance genes with both maternal and adult RM microbiomes, indicating potential vertical transmission. Comparative analysis of the metagenomes between the RM fetus and a human fetus revealed significant differences in microbial composition and genes, yet also showed similarities in certain abundant microbiota. Collectively, our results contribute to a more comprehensive understanding of the intrauterine microbial environment in macaques.

Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight the gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB axis forms a dynamic network facilitating bidirectional communication between the gastrointestinal tract, liver, and central nervous system. Dysregulation within this axis, encompassing gut dysbiosis and microbial metabolites, is emerging as a critical factor influencing PD progression. Our understanding of PD was traditionally centered on neurodegenerative processes within the brain. However, examining PD through the lens of the GLB axis provides new insights. This review provides a comprehensive analysis of microbial metabolites, such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), kynurenine, serotonin, bile acids, indoles, and dopamine, which are integral to PD pathogenesis by modulation of the GLB axis. Our extensive research included a comprehensive literature review and database searches utilizing resources such as gutMGene and gutMDisorder. These databases have been instrumental in identifying specific microbes and their metabolites, shedding light on the intricate relationship between the GLB axis and PD. This review consolidates existing knowledge and underscores the potential for targeted therapeutic interventions based on the GLB axis and its components, which offer new avenues for future PD research and treatment strategies. While the GLB axis is not a novel concept, this review is the first to focus specifically on its role in PD, highlighting the importance of integrating the liver and microbial metabolites as central players in the PD puzzle.

The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity-a state characterized by chronic inflammation and systemic dyshomeostasis-there is growing scientific and clinical interest in understanding how obesity reshapes immune function. In this review, we propose that obesity is not merely an altered metabolic state but also a fundamentally altered immunological state. We summarize key seminal and recent findings that elucidate how obesity influences immune function, spanning its classical role in microbial defense, its contribution to maladaptive inflammatory diseases such as asthma, and its impact on antitumor immunity. We also explore how obesity modulates immune function within tissue parenchyma, with a particular focus on the role of T cells in adipose tissue. Finally, we consider areas for future research, including investigation of the durable aspects of obesity on immunological function even after weight loss, such as those observed with glucagon-like peptide-1 (GLP-1) receptor agonist treatment. Altogether, this review emphasizes the critical role of systemic metabolism in shaping immune cell functions, with profound implications for tissue homeostasis across various physiological contexts.

The gut microbiota contributes to host health by facilitating nutrient uptake, digestion, energy metabolism, intestinal development, vitamin synthesis, and immunomodulation, and plays an important role in the growth and reproduction of the animal itself. Considering the paucity of research on the gut microbiota of wild snakes, this study focused on bamboo pitviper (Viridovipera stejnegeri) populations from Anhui, Guizhou, and Hunan, with multiple fecal samples collected from each population (six, five, and three, respectively). Total microbial DNA was extracted from the fecal samples using metagenomic next-generation sequencing and differences in gut microbial composition, abundance, and carbohydrate-active enzymes (CAZymes) were analyzed and compared among the three populations. Results showed no significant variance in the α-diversity of the gut microbes across the three populations, while principal coordinate analysis revealed significant differences in gut microbe composition. The four most abundant phyla in the gut microbiota of V. stejnegeri were Pseudomonadota, Bacteroidota, Actinomycetota, and Bacillota, while the four most abundant genera were Salmonella, Citrobacter, Bacteroides, and Yokenella. Linear discriminant analysis effect size demonstrated notable differences in gut microbial abundance among the three populations. Marked differences in CAZyme abundance were also observed across the microbial communities. Future studies should incorporate diverse ecological factors to evaluate their influence on the composition and function of gut microbiota.

Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.

The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.

Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.

The gut system, commonly referred to as one of the principal organs of the human "superorganism," is a home to trillions of bacteria and serves an essential physiological function in male reproductive failures or infertility. The interaction of the endocrine-immune system and the microbiome facilitates reproduction as a multi-network system. Some recent studies that link gut microbiota to male infertility are questionable. Is the gut-testis axis (GTA) real, and does it affect male infertility? As a result, this review emphasizes the interconnected links between gut health and male reproductive function via changes in gut microbiota. However, a variety of harmful (endocrine disruptors, heavy metals, pollutants, and antibiotics) and favorable (a healthy diet, supplements, and phytoconstituents) elements promote microbiota by causing dysbiosis and symbiosis, respectively, which eventually modify the activities of male reproductive organs and their hormones. The findings of preclinical and clinical studies on the direct and indirect effects of microbiota changes on testicular functions have revealed a viable strategy for exploring the GTA-axis. Although the GTA axis is poorly understood, it may have potential ties to reproductive issues that can be used for therapeutic purposes in the future.

Microbial communities play key roles across diverse environments. Predicting their function and dynamics is a key goal of microbial ecology, but detailed microscopic descriptions of these systems can be prohibitively complex. One approach to deal with this complexity is to resort to coarser representations. Several approaches have sought to identify useful groupings of microbial species in a data-driven way. Of these, recent work has claimed some empirical success at de novo discovery of coarse representations predictive of a given function using methods as simple as a linear regression, against multiple groups of species or even a single such group (the ensemble quotient optimization (EQO) approach). Modeling community function as a linear combination of individual species' contributions appears simplistic. However, the task of identifying a predictive coarsening of an ecosystem is distinct from the task of predicting the function well, and it is conceivable that the former could be accomplished by a simpler methodology than the latter. Here, we use the resource competition framework to design a model where the "correct" grouping to be discovered is well-defined, and use synthetic data to evaluate and compare three regression-based methods, namely, two proposed previously and one we introduce. We find that regression-based methods can recover the groupings even when the function is manifestly nonlinear; that multi-group methods offer an advantage over a single-group EQO; and crucially, that simpler (linear) methods can outperform more complex ones.

The prevalence of anxiety, depression, and other psychological comorbidities among patients with inflammatory bowel disease (IBD) significantly exceeds that of the general population. Moreover, a bidirectional relationship exists between psychological comorbidities and IBD. This intricate interplay has substantial clinical implications, impacting treatment adherence, therapeutic efficacy, and disease recurrence rates. In this review, we explore the multifaceted mechanisms through which psychological factors influence IBD progression, treatment response, and prognosis. Specifically, we delve into the involvement of the hypothalamic-pituitary-adrenal axis, autonomic nervous system, enteric nervous system, microbiota-gut-brain axis, systemic inflammatory cytokines, and immune cell function. Additionally, we discuss the potential benefits of antidepressant therapy in mitigating IBD risk and the role of psychotropic drugs in reducing peripheral inflammation. Recognizing and addressing psychological comorbidity is pivotal in comprehensive IBD management. We advocate for the integration of biopsychosocial approaches into IBD treatment strategies, emphasizing the need for innovative psychological interventions as adjuncts to conventional therapies. Rigorous research investigating the impact of antidepressants and behavioral interventions on IBD-specific outcomes may herald a paradigm shift in IBD management.

Background: The oral microbiota is the second largest microbial community in humans. It contributes considerably to microbial diversity and health effects, much like the gut microbiota. Despite physical and chemical barriers separating the oral cavity from the gastrointestinal tract, bidirectional microbial transmission occurs between the two regions, influencing overall host health. Method: This review explores the intricate interplay of the oral-gut-brain axis, highlighting the pivotal role of the oral microbiota in systemic health and ageing, and how it can be influenced by diet. Results: Recent research suggests a relationship between oral diseases, such as periodontitis, and gastrointestinal problems, highlighting the broader significance of the oral-gut axis in systemic diseases, as well as the oral-gut-brain axis in neurological disorders and mental health. Diet influences microbial diversity in the oral cavity and the gut. While certain diets/dietary components improve both gut and oral health, others, such as fermentable carbohydrates, can promote oral pathogens while boosting gut health. Conclusions: Understanding these dynamics is key for promoting a healthy oral-gut-brain axis through dietary interventions that support microbial diversity and mitigate age-related health risks.

Akkermansia muciniphila (A. muciniphila) is a promising candidate bacterium for stress management due to its beneficial effects on the microbiota-gut-brain axis (MGBA). As a well-known mucin-degrading bacterium in the digestive tract, A. muciniphila has demonstrated significant benefits for host physiology. Recent research highlights its potential in treating several neuropsychiatric disorders. Proposed mechanisms of action include the bacterium's outer membrane protein Amuc_1100 and potentially its extracellular vesicles (EVs), which interact with host immune receptors and influence serotonin pathways, which are crucial for emotional regulation. Despite its potential, the administration of probiotics containing A. muciniphila faces technological challenges, prompting the development of pasteurized forms recognized as safe by the European Food Safety Authority (EFSA). This review systematically examines the existing literature on the role of A. muciniphila in stress management, emphasizing the need for further research to validate its efficacy. The review follows a structured methodology, including comprehensive database searches and thematic data analysis, to provide a detailed understanding of the relationship between stress, microbiota, and A. muciniphila therapeutic potential.

The gut microbiome plays a crucial role in host health throughout the lifespan by influencing brain function during aging. The microbial diversity of the human gut microbiome decreases during the aging process and, as a consequence, several mechanisms increase, such as oxidative stress, mitochondrial dysfunction, inflammatory response, and microbial gut dysbiosis. Moreover, evidence indicates that aging and neurodegeneration are closely related; consequently, the gut microbiome may serve as a novel marker of lifespan in the elderly. In this narrative study, we investigated how the changes in the composition of the gut microbiome that occur in aging influence to various neuropathological disorders, such as mild cognitive impairment (MCI), dementia, Alzheimer's disease (AD), and Parkinson's disease (PD); and which are the possible mechanisms that govern the relationship between the gut microbiome and cognitive impairment. In addition, several studies suggest that the gut microbiome may be a potential novel target to improve hallmarks of brain aging and to promote healthy cognition; therefore, current and future therapeutic interventions have been also reviewed.

In the search for the origin of Amyotrophic Lateral Sclerosis disease (ALS), we hypothesized earlier (Monselise, 2019) that D-amino acids produced by stressed microbiome may serve as inducers of the disease development. Many examples of D-amino acid accumulation under various stress conditions were demonstrated in prokaryotic and eukaryotic cells. In this work, wild-type Escherichia coli, members of the digestive system, were subjected to carbon and nitrogen starvation stress. Using NMR and LC-MS techniques, we found for the first time that D-glutamate accumulated in the stressed bacteria but not in control cells. These results together with the existing knowledge, allow us to suggest a new insight into the pathway of ALS development: D-glutamate, produced by the stressed microbiome, induces neurobiochemical miscommunication setting on C1q of the complement system. Proving this insight may have great importance in preventive medicine of such MND modern-age diseases as ALS, Alzheimer, and Parkinson.

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity.

Acute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide, driven by complex and multifaceted etiological factors. Metabolic dysregulation, gastrointestinal microbiome alterations, and systemic inflammation are emerging as significant contributors to AIS pathogenesis. This review addresses the critical need to understand how these factors interact to influence AIS risk and outcomes. We aim to elucidate the roles of dysregulated adipokines in obesity, the impact of gut microbiota disruptions, and the neuroinflammatory cascade initiated by lipopolysaccharides (LPS) in AIS. Dysregulated adipokines in obesity exacerbate inflammatory responses, increasing AIS risk and severity. Disruptions in the gut microbiota and subsequent LPS-induced neuroinflammation further link systemic inflammation to AIS. Advances in neuroimaging and biomarker development have improved diagnostic precision. Here, we highlight the need for a multifaceted approach to AIS management, integrating metabolic, microbiota, and inflammatory insights. Potential therapeutic strategies targeting these pathways could significantly improve AIS prevention and treatment. Future research should focus on further elucidating these pathways and developing targeted interventions to mitigate the impacts of metabolic dysregulation, microbiome imbalances, and inflammation on AIS.

The human microbiota plays a key role in cancer diagnosis, pathogenesis, and treatment. However, osteosarcoma-associated oral microbiota alterations have not yet been unraveled. The aim of this study was to explore the characteristics of oral microbiota in osteosarcoma patients compared to healthy controls, and to identify potential microbiota as a diagnostic tool for osteosarcoma.

The oral microbiota was analyzed in osteosarcoma patients (n = 45) and matched healthy controls (n = 90) using 16S rRNA MiSeq sequencing technology.

The microbial richness and diversity of the tongue coat were increased in osteosarcoma patients as estimated by the abundance-based coverage estimator indices, the Chao, and observed operational taxonomy units (OTUs). Principal component analysis delineated that the oral microbial community was significant differences between osteosarcoma patients and healthy controls. 14 genera including Rothia, Halomonas, Rhodococcus, and Granulicatella were remarkably reduced, whereas Alloprevotella, Prevotella, Selenomonas, and Campylobacter were enriched in osteosarcoma. Eventually, the optimal four OTUs were identified to construct a microbial classifier by the random forest model via a fivefold cross-validation, which achieved an area under the curve of 99.44% in the training group (30 osteosarcoma patients versus 60 healthy controls) and 87.33% in the test group (15 osteosarcoma patients versus 30 healthy controls), respectively. Notably, oral microbial markers validated strong diagnostic potential distinguishing osteosarcoma patients from healthy controls.

This study comprehensively characterizes the oral microbiota in osteosarcoma and reveals the potential efficacy of oral microbiota-targeted biomarkers as a noninvasive biological diagnostic tool for osteosarcoma.

Wnt/β-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis.

Proteins and target genes of both pathways were analysed by RT-qPCR and IHC in tissues from healthy faecal immunochemical test positive (FIT+, n = 17), FAP (n = 17) and CRC (n = 15) subjects. CRC-related mutations were analysed through NGS and Sanger. Oral, faecal and mucosal microbiota was profiled by 16 S rRNA-sequencing.

We found simultaneous hyperactivation of Wnt/β-catenin and PI3K/mTOR pathways in FAP-lesions compared to CRCs. Wnt/β-catenin molecular markers positively correlated with Clostridium_sensu_stricto_1 and negatively with Bacteroides in FAP faecal microbiota. Alistipes, Lachnospiraceae, and Ruminococcaceae were enriched in FAP stools and adenomas, the latter also showing an overabundance of Lachnoclostridium, which positively correlated with cMYC. In impaired-mTOR-mutated CRC tissues, p-S6R correlated with Fusobacterium and Dialister, the latter also confirmed in the faecal-ecosystem.

Our study reveals an interplay between Wnt/β-catenin and PI3K/mTOR, whose derangement correlates with specific microbiota signatures in FAP and CRC patients, and identifies new potential biomarkers and targets to improve CRC prevention, early adenoma detection and treatment.

Lavender, an aromatic plant with a history dating back to ancient Egypt and Greece, is consumed because of its diverse pharmacological properties, including sedation, sleep aid, and antidepressant effects. However, the mechanisms underlying these antidepressant properties remain unclear. In this study, we explored the impact of lavender essential oil (LEO) inhalation on the diversity of gut microbiota, metabolites, and differential gene expression in the hippocampus of alcohol-withdrawn depressive rats. Additionally, we examined alterations in the hippocampal transient receptor potential (TRP) channel-mediated inflammatory regulation within the brain-gut axis of depressive rats. The results demonstrated a significant decrease in sucrose preference, diminished activity in the central zone of the open field test, and prolonged immobility time in the forced swim test in alcohol-withdrawn depressive rats, indicating the amelioration of depressive states following lavender essential oil inhalation. 16 S rDNA sequencing analysis revealed a significant reduction in Bacteroidota and Muribaculaceae in the gut of alcohol-withdrawn depressive rats, whereas lavender essential oil significantly increased the relative abundance of Muribaculaceae and other bacterial species. Metabolomic analysis identified 646 distinct metabolites as highly correlated biomarkers between the model and lavender essential oil groups. Furthermore, lavender essential oil inhalation significantly attenuated hippocampal inflammatory factors IL-2, IL-6, IL-1β, and TNF-α. This study identified elevated expression of Trpv4 and Calml4 in the hippocampal region of alcohol-withdrawn depressed rats and showed that lavender essential oil inhalation regulated aberrantly expressed genes. Our research suggests that lavender essential oil downregulates Trpv4, modulates inflammatory factors, and alleviates depressive-like behavior in alcohol withdrawal rats.

We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, two months, and six months to assess antibiotic and probiotic exposure. Gut microbiotas were sequenced via 16S rRNA, and ARGs were conducted by qPCR, including beta-lactam (mecA, blaTEM), tetracycline (tetM), fluoroquinolone (qnrS), aminoglycoside (aac(6')-Ib), and macrolide (ermB). Infants were categorized by antibiotic and probiotic usage and stratified by delivery mode, microbial composition, and ARG abundances were compared, and potential correlations were explored. A total of 189 fecal samples were analyzed in this study. The gut microbiota diversity (Chao1 index) was significantly lower in the "only probiotics" (PRO) group compared to the "neither antibiotics nor probiotics" (CON) group at six months for the CS stratification (p = 0.029). Compositionally, the abundance of core genus Bifidobacterium_pseudocatenulatum was less abundant for the antibiotic during delivery (IAP) group than that in the CON group within the first three days (p = 0.009), while core genus Enterococcus_faecium was more abundant in the PRO than that in the CON group (p = 0.021) at two months. ARGs were highly detected, with Enterococcus hosting tetM and Escherichia associated with blaTEM within three days of birth, though no correlation was found between Bifidobacterium and ARGs. These findings emphasized the critical importance of carefully managing antibiotic and probiotic exposures in early life, with implications for promoting lifelong health through preserving a healthy infant gut ecosystem.

Inter-individual human variability, driven by various genetic and environmental factors, complicates the ability to develop effective population-based early disease detection, treatment and prognostic assessment. The microbiome, consisting of diverse microorganism communities including viruses, bacteria, fungi and eukaryotes colonizing human body surfaces, has recently been identified as a contributor to inter-individual variation, through its person-specific signatures. As such, the microbiome may modulate disease manifestations, even among individuals with similar genetic disease susceptibility risks. Information stored within microbiomes may therefore enable early detection and prognostic assessment of disease in at-risk populations, whereas microbiome modulation may constitute an effective and safe treatment tailored to the individual. In this Review, we explore recent advances in the application of microbiome data in precision medicine across a growing number of human diseases. We also discuss the challenges, limitations and prospects of analysing microbiome data for personalized patient care.

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established. Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS. In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS. Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.

The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging. This chronic inflammatory state, also known as inflammaging, induced by the chronic activation of the innate immune system via the macrophage, is controlled by the gut microbiota, which links nutrition, metabolism, and the innate immune response. Here, we present the functional roles of prebiotics, probiotics, synbiotics, and postbiotics as bioactive compounds by underscoring their putative contributions to (1) the reduction in gut hyperpermeability due to lipopolysaccharide (LPS) inactivation, (2) increased intestinal barrier function as a consequence of the upregulation of tight junction proteins, and (3) inhibition of proinflammatory pathways, overall leading to the alleviation of chronic inflammation in the management of obesity.