Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can subsequently affect bone metabolism. Moreover, microbiome-related metabolites may have important effects on bone metabolism. We aim to review the relationships among the GM, microbial metabolites, and bone metabolism and to summarize the potential mechanisms involved and the theory of the gut‒bone axis. We also describe existing bottlenecks in laboratory studies, as well as existing challenges in clinical settings, and propose possible future research directions.

Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.

In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.

The gut microbiota has been linked to a number of neurological disorders. However, it is unclear whether the gut microbiota is involved in the genesis of chronic itch, a refractory condition that afflicts patients both physically and mentally. Here, we report that depletion of gut microbiota enhances tolerance to itch in mice orally administered with antibiotics (ABX) and mice free of germ. Of note, oral gavage with Bacteroides fragilis (B. fragilis), a prominent species of the genus Bacteroides with most differential change, corrected the ABX-induced itch dysfunction through its driven metabolite acetyl-l-carnitine (ALC). Mechanistically, gut microbiota or B. fragilis depletion caused a decrease in RNA N6-methyladenosine (m6A) demethylase FTO expression in the dorsal horn and a consequent increase in RNA m6A sites in Mas-related G protein-coupled receptor F (MrgprF) mRNA, leading to decreased MRGPRF protein. The downregulation of FTO was triggered by inactivation of ETS proto-oncogene 1 (ETS1), a transcription factor that binds to the Fto promoter. These findings support a gut microbe - spinal connection in modulation of itch sensation in RNA m6A epigenetic-dependent manner and highlight a critical role of ALC in linking the altered B. fragilis and itch dysfunction.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.

Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.

The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response and fibrosis is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via infection with the pathogenic bacterial species enterotoxigenic Bacteroides fragilis (ETBF) and implanted particulate material (mean particle size <600 μm) of the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and γδ T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation, increased levels of neutrophils in lymphoid tissues, and altered skeletal muscle gene expression. At the PCL implant site, we found significant changes in the transcriptome of sorted stromal cells between infected and control mice, including differences related to ECM components such as proteoglycans and glycosaminoglycans. However, we did not observe ETBF-induced differences in fibrosis levels. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant.

Elucidating the specific processes and drivers of community assembly in the host microbiome is essential to fully understand host biology. Toward this goal, an important first step is to describe co-occurrence patterns among different microbial taxa, which can be driven by numerous factors, such as host identity. While host identity can be an important influential factor on co-occurrence patterns, a limited number of studies have explored the relative importance of host identity after controlling for other environmental factors. Here, we examined microbial co-occurrence patterns in four phylogenetically distinct trematode species living within the same snail species, collected concomitantly from the same habitat. Our previous study determined that all these trematodes shared some bacterial taxa, and the relative abundance of microbial taxa differed among trematodes, possibly due to differences in their eco-physiological traits. Here, we specifically predict that pairwise microbial co-occurrence patterns also vary among trematode host species. Our results showed that co-occurrence patterns among eight microbial families varied greatly among the four trematode hosts, with some microbial families co-occurring in some trematode species, whereas no such patterns were observed in other trematodes. Our study suggests that the habitat identity (trematode species) and its associated biotic characteristics, such as physiological and ecological traits, can determine co-occurrence patterns among microbial taxa, with substantial effects on local community composition.

Probiotics such as Lactobacillus and Bifidobacterium spp. have been shown to be critical for maintaining host homeostasis. In recent years, key compounds of postbiotics derived from probiotic metabolism and cellular secretion have been identified for their role in maintaining organ immunity and regulating intestinal inflammation. In particular, probiotic-derived extracellular vesicles (PEVs) can act as postbiotics, maintaining almost the same functional activity as probiotics. They also have strong biocompatibility and loading capacity to carry exogenous or parental active molecules to reach distal organs to play their roles. This provides a new direction for understanding the intrinsic microbiota-host communication mechanism. However, most current studies on PEVs are limited to their functional effects/benefits, and their specific physicochemical properties, composition, intrinsic mechanisms for maintaining host homeostasis, and possible threats remain to be explored. Here, we review and summarize the unique physicochemical properties of PEVs and their bioactivities and mechanisms in mediating microbiota-host communication, and elucidate the limitations of the current research on PEVs and their potential application as postbiotics.

Nowadays, understanding the biotic responses to the enhanced urbanization need to encompass not the only the physiological and phenotypic features but also the related microbiota of wildlife animals. One of main threats in urban ecosystems is the chemical pollution. Thus, we have explored whether the cloacal microbiota of feral pigeons (Columba livia) is impacted by both their geographical foraging area, and metal exposure in an urban context. First, pigeons were captured in 4 specific areas of Paris (France) and placed in captivity. By applying a 16SrRNA metabarcoding approach, we observed that the gut microbiota diversity was structured according to the capture sites, with strong variation of Actinobacteria, Bacilli and Clostridia, that could be linked to the granivorous or low-protein diets. Subsequently, we experimentally exposed these pigeons to zinc and/or lead (two-factor cross design) during 90 days in a non-urban environment, but no impact on the composition nor diversity of pigeon gut microbiota, has been observed after 45 and 90 days of metal exposures. However, the composition and diversity significantly differed from the microbiota at the capture period, with the emergence of taxa belonging to Corynebacterium and Bifidobacterium in captive conditions. These data highlight a strong impact of the lifestyles (captivity in non-urban environment) on the gut microbiota composition. In parallel, we hypothesized that the diet and the local environment might have smoothed the impact of the metal exposure for pigeons that could quickly change the structure of their gut microbiota. Our findings shed light on the effects of urban pollution and environment on bird communities, that can be extended to their gut microbiota causing potential additive or synergic negative effects to host organisms and populations.

The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analyzed the fecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted fecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory performance, whereas FMT from mice housed in SOPF facility did not induce memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born animals in a conventional facility resulted in the reappearance of specific microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show a strong impact of housing conditions on microbiota-associated phenotypes and question the relevance of breeding preclinical models in specific pathogen-free (SPF) facilities.

Housing conditions affect the composition of the gut microbiota. Gut microbiota of 6-month-old conventionally bred Alzheimer's mice is dysbiotic. Gut dysbiosis is absent in Alzheimer's mice housed in highly sanitized facilities. Transfer of fecal microbiota from conventionally bred mice affects cognition. Microbiota of mice housed in highly sanitized facilities has no effect on cognition.

Neurodevelopment is a multifaceted and tightly regulated process essential for the formation, maturation, and functional specialization of the nervous system. It spans critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, which collectively establish the foundation for cognitive, behavioral, and emotional functions. Metabolism serves as a cornerstone for neurodevelopment, providing the energy and substrates necessary for biosynthesis, signaling, and cellular activities.

Key metabolic pathways, including glycolysis, lipid metabolism, and amino acid metabolism, support processes such as cell proliferation, myelination, and neurotransmitter synthesis. Crucial signaling pathways, such as insulin, mTOR, and AMPK, further regulate neuronal growth, synaptic plasticity, and energy homeostasis. Dysregulation of these metabolic processes is linked to a spectrum of neurodevelopmental disorders, including autism spectrum disorders (ASDs), intellectual disabilities, and epilepsy.

This review investigates the intricate interplay between metabolic processes and neurodevelopment, elucidating the molecular mechanisms that govern brain development and the pathogenesis of neurodevelopmental disorders. Additionally, it highlights potential avenues for the development of innovative strategies aimed at enhancing brain health and function.

The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3-/- (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3-/- mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3-/- mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3-/- mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.

The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.

Microbes massively colonize the mammalian newborn at birth. We previously reported that the microbiota influences key neurodevelopmental events, e.g., when compared to their conventionally colonized (CC) counterparts, sterile newborn mice ("germ-free" or GF) show higher cell death in the hypothalamic paraventricular nucleus (PVN). Here, we tested the hypothesis that the microbiota, perhaps via cell death mechanisms, shapes PVN development. To this aim, we used a cross-fostering approach that also allowed us to test whether any potential effects are influenced by microbial colonization at birth or programmed prenatally via the maternal microbiota. Specifically, we cross-fostered GF pups to CC dams (GF → CC) immediately after birth and compared them to control groups cross-fostered within microbial status (CC → CC, GF → GF). At postnatal day 7, GF → GF and GF → CC newborns had fewer PVN cells than did CC → CC newborns, without affecting PVN volume. In a follow-up experiment, we confirmed a reduction in PVN cell number with no change in PVN volume in adult GF mice. Thus, the greater cell death previously observed in the PVN of newborn GF mice is associated with a permanent reduction in cell number. Because the deficit is not altered by introducing a microbiota at birth, our findings also suggest that the maternal microbiota shapes development of the PVN starting in utero.

The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.

Parkinson's disease (PD) and sarcopenia are prevalent age-related conditions that often coexist in affected individuals. Sarcopenia is particularly common among PD patients, with severe cases affecting approximately one in five individuals with the disease. Furthermore, sarcopenia is closely linked to the accelerated progression of PD, diminished quality of life, greater susceptibility to falls and fractures, and increased mortality risk. Although the precise mechanisms remain unclear, numerous studies suggest that factors such as the accumulation of α-Synuclein in skeletal muscle, loss of motor neurons, inflammation, phosphate toxicity, hormonal dysregulation, vitamin D deficiency, intestinal flora imbalances, and dysfunction of the gut-muscle-brain axis contribute to sarcopenia in PD. Understanding these mechanisms provides valuable insights into the relationship between PD and sarcopenia and establishes a foundation for future research and therapeutic strategies. This review examines the mechanisms underlying sarcopenia in PD, methods for its screening and assessment, and potential avenues for future research, including strategies for risk reduction and treatment.

Alzheimer's disease (AD), which is a chronic neurodegenerative disorder, is marked by the progressive deteriorations in learning and memory capabilities. The microbiota-gut-brain axis has come to be regarded as a crucial element in relation to the pathogenesis as well as the treatment of AD. Eucommiae cortex polysaccharides (EPs), being among the most plentiful substances present in the Eucommiae cortex, show the potential to exert immunomodulatory and neuroprotective function. However, whether EPs are protective against AD and their mechanism of action remain to be investigated OBJECTIVES: We hypothesize that EPs can regulate brain glutamine metabolism through gut microbiota and the butyric acid metabolized by them, improve oxidative stress and autophagy in the brain, and thus alleviate AD.

In the present study, we used EPs (0.25 % w/w in food) and fecal microbiota transplantation, as well as butyrate supplementation (0.1 M in water), to intervene in AD mice. Multi-omics were used to determine the mechanism by which EPs improve AD-related learning and memory impairments.

Our results suggest that EPs, functioning as a prebiotic, alleviated learning and memory impairments in AD mice. Mechanistically, EPs are able to reshape the gut microbiota, promote the growth of gut microbiota involved in short-chain fatty acid metabolism, particularly butyrate-producing microbes. The butyrate produced by these microbes improves the brain microenvironment by modulating oxidative stress and autophagy mediated by brain glutamate metabolism, improving learning and memory impairments in AD mice, and inhibiting the formation and deposition of beta-amyloid proteins. Fecal microbiota transplantation (FMT) and butyrate supplementation further confirm this conclusion.

Our results highlighted that EPs can alleviate learning and memory impairments in AD with a gut microbiota-dependent manner and that butyric acid metabolized by butyric acid-metabolizing bacteria in the gut plays a central role in regulating brain glutamine metabolism to improve brain microenvironmental homeostasis. Meanwhile, the present study provides new insights into the treatment of AD with natural products.

Brain development involves the sequential expression of vulnerable biological processes including cell proliferation, programmed cell death, neuronal migration, synapse and functional unit formation. All these processes involve gene and activity-dependent events that can be distorted by many extrinsic and intrinsic environmental factors, including stress, microbiota, inflammatory signals, hormonal signals and epigenetic factors, hence leading to disorders born in the womb that are manifested later in autism spectrum disorders (ASDs) and other neurodevelopmental disorders. Predicting and treating such disorders call for a conceptual framework that includes all aspects of developmental biology. Here, taking the high incidence of ASDs as an example, we first discuss the intrinsic limitations of the genetic approach, notably the widely used twin studies and SNPs. We then review the long list of in utero events that can deviate developmental sequences, leading to persistent aberrant activity generated by immature misplaced and misconnected neuronal ensembles that are the direct cause of ASD. In a clinical perspective, we suggest analysing non-genetic maternity data to enable an early prediction of babies who will develop ASD years later, thereby facilitating early psycho-educative techniques. Subsequently, agents capable of selectively silencing malformed immature networks offer promising therapeutic perspectives. In summary, understanding developmental processes is critical to predicting, understanding and treating ASD, as well as most other disorders that arise in the womb.

The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.

Patients experience both positive and negative changes in mood following bariatric surgery and mental health outcomes have been reported to differ between procedure types. Understanding changes in symptoms over time and between surgical procedures is vital to providing meaningful, long-term, patient-centered care.

To examine the nature and time course of changes in depressive symptoms after different bariatric procedures.

Medline, Embase, Emcare, PsycINFO, CINAHL, and CENTRAL databases were systematically searched from inception to January 18, 2024. Ninety publications describing patient-reported depressive symptoms in 13,146 individuals undergoing bariatric procedures were included.

Qualitative analysis indicated a reduction of depressive symptoms at all time points following all bariatric procedure types. However, a subset of patients experienced worsening symptoms post-surgery. Meta-analyses indicated depressive symptoms improve following bariatric surgery by an SMD of -0.6 (95% CI: -0.8, -0.4) in the short term (0-4 months post-surgery), -0.9 (95% CI: -1.0, -0.8) in the medium term (5-12 months), and -0.7 (95% CI: -0.9, -0.5) in the long term (> 12 months). There was no evidence that surgery type was associated with the change in depressive symptoms at any time point post-surgery.

Patient-reported depressive symptoms improve following bariatric surgery with improvements peaking in the medium term and diminishing over time. Significant heterogeneity in the results cannot be explained by surgery type, baseline depression, or depression instrument used across studies. Long-term management of post-bariatric surgery patients must consider the potential for adverse psychological effects of surgery.

Obesity is associated with impaired hippocampal-dependent memory, but the mechanisms driving this pathology are not fully understood. Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory. However, there is need for a more detailed description of the pathways by which WD may impair memory. The short vs long-term effect of specific dietary components on brain structure and functions as well as the precise mechanism and molecular pathways involved are still not fully understood. This review focuses on the mechanisms and effects of gut microbiota-driven neuroinflammation. WD leads to changes and imbalance in bacterial taxa abundances that are deleterious to the host health (gut dysbiosis) and studies in rodent models show these changes are sufficient to impair hippocampal-dependent memory. Here, we discuss a variety of proposed mechanisms linking microbiota composition to hippocampal function, with a focus on neuroinflammation. Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation.

Ginsenoside compound K (CK) exhibits neuroprotective properties; however, the underlying mechanisms behind these effects have not been investigated thoroughly. CK is the primary active compound derived from ginseng and is metabolized in the gut. It enhances neuronal function by modulating the gut microflora. Therefore, the present study aimed to elucidate the mechanism through which CK enhances cognitive function, employing gut microbiome and microarray analyses. The results revealed that CK upregulated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), suppressed amyloid-β (Aβ) aggregation in hippocampal neurons, and influenced the expression of cyclin-dependent kinase-5 (CDK5), (including insulin receptor substrate 2) IRS2, insulin-degrading enzyme (IDE), glycogen synthase kinase-3 beta (GSK-3β), glucose transporter type 1 (GLUT1), and glucose transporter type 3 (GLUT3) proteins. These proteins play crucial roles in regulating brain glucose metabolism, increasing neuronal energy, and reducing neuronal apoptosis, thereby ameliorating cognitive impairment in mice.

Neuroangiostrongyliasis is characterized by eosinophilic meningoencephalitis with a robust onset of severe neurological symptoms, by which immunological factors and peripheral metabolites have been postulated to affect the course of the disease. The gut-brain axis provides a bidirectional communication between the gut and the central nervous system, and therefore, understanding the gut microbiome may provide us with a deeper insight into the pathogenesis of angiostrongyliasis. Using 16S rRNA sequencing, we identified an increase in the abundance of different Lactobacillus species in Angiostrongylus cantonensis-infected mice, which was correlated to the disease severity. However, attempts to inoculate L. johnsonii into A. cantonensis-infected mice surprisingly revealed an improvement in neuroinflammation and prolonged survival. RNA sequencing suggested an immune-modulatory effect of L. johnsonii, which was confirmed by ELISA, showing increased levels of IL-10 and reduced levels of IL-2, IL-4, IL-5, and MCP-1 in the brain. Nevertheless, L. johnsonii-associated improvements were not associated with microbiome-related metabolites, as UHPLC-MS/MS analysis revealed no change in short-chain fatty acids, tryptophan metabolites, and bile acids. Our results suggest that while intestinal L. johnsonii appears to be linked to the progression of neuroangiostrongyliasis, these bacteria are likely attempting to modulate the dysregulated immune response to combat the disease. This is one of the first studies to investigate the gut microbiome in mice with A. cantonensis infection, which extends our knowledge from the microbiome-point-of-view of the pathogenesis of angiostrongyliasis and how the body defends against A. cantonensis. This work also extends to possible treatment approaches using L. johnsonii as probiotics.

The gut microbiota influences human and animal cognition and behaviour through its effects on the endocrine and immune systems. The microbiome-behaviour relationship may be especially relevant for fish, due to their diverse evolutionary history and potential implications for farming and conservation. Yet, there is limited research on the interaction between gut microbiome and behaviour in non-model fish. We manipulated the rearing environment and diet of fish from two inbred strains of the self-fertilizing mangrove killifish (Kryptolebias marmoratus) and assessed the effects on the gut microbiome and its interactions with anxiety-like behaviours. We found that microbiota composition and alpha diversity were significantly influenced by host genetics (strain), hatching mode (naturally or artificial dechorionation) and diet, but not by environmental enrichment. Fish activity level and inspections of a novel object were strongly associated with microbiota community composition and alpha diversity. The microbial taxa associated with differences in behaviour were dominated by Bacteroidales, potentially related to the production of metabolites affecting neural development. We suggest that the association between microbiome and fish behaviour could be an indirect effect of the modulation of the gut microbiota by host genetics and early rearing conditions, which could be affecting the production of microbial metabolites that interact with the fish physiology.

Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.

Circadian rhythms are innate biological systems that control everyday behavior and physiology. Furthermore, bilateral interaction between the host's circadian rhythm and the gut microbes influences a variety of health ramifications, including metabolic diseases, obesity, and mental health including GALT physiology and the microbiome population. Therefore, we are studying the correlation between differential gene expression in the chicken brain and microbiota abundance during circadian rhythms. To understand this, we raised freshly hatched chicks under two photoperiod treatments: normal photoperiod (NP = 12/12 LD) and extended photoperiod (EP 23/1 LD). The chicks were randomly assigned to one of two treatments. After 21 days of circadian entrainment, the chicks were euthanized at nine time points spaced six hours apart over 48 h to characterize the brain transcriptomes. Each sample's RNA was extracted, and 36 mRNA libraries were generated and sequenced using Illumina technology, followed by data processing, count data generation, and differential gene expression analysis. We generated an average of 17.5 million reads per library for 237.9 M reads. When aligned to the Galgal6 reference genome, 11,867 genes had detectable expression levels, with a common dispersion value of 0.105. To identify the genes that follow 24 h rhythms, counts per million data were performed in DiscoRhythm. We discovered 577 genes with Cosinor and 417 with the JTK cycle algorithm that exhibit substantial rhythms. We used weighted gene co-expression network analysis (WGCNA) to analyze the correlation between differentially expressed genes and microbiota abundance. The most enriched pathways included aldosterone-regulated sodium reabsorption, endocrine and other factor-regulated calcium reabsorption, GABAergic synapse, oxidative phosphorylation, serotonergic synapse, dopaminergic synapse and circadian entrainment. This study builds on our previous study, and adds new findings about the specific interactions and co-regulation of the brain transcriptome and the gut microbiota. The interaction between gut microbiota and host gene expression highlights the potential benefits of microbiome-modulation approaches to improve gut health and performance in poultry.

Microglia and astrocytes are the primary glial cells in the central nervous system (CNS) and their function is shaped by multiple factors. Regulation of CNS glia by the microbiota have been reported, although the role of specific bacteria has not been identified. We colonized germ-free mice with the type strain Akkermansia muciniphila (AmT) and a novel A. muciniphila strain BWH-H3 (Am-H3) isolated from a subject with multiple sclerosis and compared to mice colonized with Bacteroides cellulosilyticus strain BWH-E5 (Bc) isolated from a healthy control subject. We then investigated the effect of these bacteria on microglia and astrocyte gene expression by RNA sequencing. We found altered gene expression profiles in brain microglia, with Akkermansia downregulating genes related to antigen presentation and cell migration. Furthermore, we observed strain specific effects, with Akkermansia H3 upregulating histone and protein binding associated genes and downregulating channel and ion transport genes. Astrocyte pathways that were altered by Akkermansia H3 mono-colonization included upregulation of proliferation pathways and downregulation in cytoskeletal associated genes. Furthermore, animals colonized with type strain Akkermansia and strain H3 had effects on the immune system including elevated splenic γδ-T cells and increased IFNγ production in CD4 + T cells. We also measured intestinal short chain fatty acids and found that both A. muciniphila strains produced proprionate while B. cellulosilyticus produced acetate, proprionate, and isovalerate. Taken together, our study shows that specific members of the intestinal microbiota influence both microglial and astroyctes which may be mediated by changes in short chain fatty acids and peripheral immune signaling.

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.

The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.

We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.

We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.

Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological α-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological α-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.

Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.

1. The avian gut hosts a complex and dynamic microbial ecosystem, which is essential for regulating host organ function. However, the relationship between the gut microbiota and the hypothalamic axis in acute stress vulnerability in ducks remains unclear.2. This study investigated how the gut microbiota affects microbial metabolism and the host stress response by comparing hypothalamic neurotransmitter availability, microbial composition and co-metabolites generated by both the microbiota and hypothalamus in ducks exhibiting the lowest active avoidance (LAA) and highest active avoidance (HAA) behaviour.3. The HAA group experienced a significant increase in the availability of arginine, histidine, glutamine, norepinephrine, L-tyrosine and melatonin during acute stress in the hypothalamus, compared to that in the LAA group. The 16S rRNA sequencing revealed significant differences in the gut microbiota composition based on acute stress vulnerabilities.4. Both caecal and hypothalamic metabolomic analyses identified 71 metabolites altered in caecal content and 95 in the hypothalamus. There was significant enrichment in pathways such as the cGMP-PKG signalling, dopaminergic synapse and endocrine resistance.5. Correlation analyses demonstrated that certain co-metabolites, including 1,3-dicyclohexylurea, 1-deoxyvaleric acid, 2-amino-2-methyl-1,3-propanediol, 3-chloroaniline, methenamine, N4-acetylcytidine-triphosphate and traumatin, may play a role in the gut microbiota-hypothalamic axis.6. The results suggested that the gut microbiome influenced acute stress responses. This provided a basis for understanding gut-hypothalamic communication and its impact on behaviour in ducks.

In the last decade, it has been discovered that intestinal flora can affect various organ-specific cancers by altering the body's energy balance, synthesizing genetic toxins and small signaling molecules, and initiating and modulating immune responses. In this review, we will focus on elucidating the role of intestinal flora based on its molecular mechanisms and its possible impact on head and neck cancers in the near future, and explore how it may be a novel approach to treating head and neck cancers in the future.

Gut microbiota dysbiosis is associated with multiple sclerosis (MS), but the causal relationship between specific gut bacteria and MS pathogenesis remains poorly understood. Therefore, we profiled the stool microbiome of people with MS (PwMS) and healthy controls (HC) using shotgun metagenomic sequencing. PwMS showed a distinct microbiome compared to HC, with Prevotella copri (PC) and Blautia species as drivers of microbial communities in HC and PwMS, respectively. Administration of MS-driving Blautia species (Blautia wexlerae; BW) to mice resulted in increased levels of gut inflammatory markers and altered microbiota with increased capacity to induce proinflammatory cytokines. Utilizing experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we identified a lower gut Bifidobacterium to Akkermansia ratio as a hallmark of the disease. BW-administered mice also showed a lower Bifidobacterium to Akkermansia ratio pre-EAE induction which correlated with increased disease severity post-EAE induction. The importance of the Bifidobacterium to Akkermansia ratio at the species level, lower Bifidobacterium adolescentis to Akkermansia muciniphila (BA:AM), was validated in our MS cohort and a large International Multiple Sclerosis Microbiome Study. Thus, our findings highlight the BA:AM ratio as a potential gut microbial marker in PwMS, opening avenues for microbiome-based diagnosis, prognosis, and therapy in MS.

Accumulating evidence suggests the microbiota is a key factor in Disorders of Gut-Brain Interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization.

We employed a combination of gnotobiotic and state-of-the-art microbial tools, behavioral analysis, immune and pharmacological approaches. Germ-free wild type, TLR signaling-deficient MyD88-/- Ticam1-/- and lymphocyte-deficient SCID mice were studied before and after colonization with specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent or transient colonizers). TLR agonists and antagonists, CCR7 antagonist or immunomodulators were used to study immune pathways. We assessed brain c-Fos, brain-derived neurotrophic factor, and dendritic and glial cells by immunofluorescence, expression of neuroimmune genes by NanoString and performed brain proteomics.

Bacterial monocolonization, conventionalization or administration of microbial products to germ-free mice altered mouse behavior similarly, acting through Toll-like receptor or nucleotide-binding oligomerization domain signaling. The process required CD11b+CD11c+CD103+ dendritic cell activation and migration into the brain. The change in behavior did not require the continued presence of bacteria and was associated with activation of multiple neuro-immune networks in the gut and the brain.

Changes in neural plasticity occur rapidly upon initial gut microbial colonization and involve innate immune signaling to the brain, mediated by CD11b+CD11c+CD103+ dendritic cell migration. The results identify a new target with therapeutic potential for DGBIs developing in context of increased gut and blood-brain barrier permeability.

A growing body of evidence suggests that the gut microbiome may contribute to changes in brain morphology. The microbiota-gut-brain axis (MGBA) has been shown to influence neurogenesis, axon myelination, and synapse structure. However, it remains unclear whether the MGBA can influence the morphology and density of inhibitory GABAergic interneurons. The aim of this study was to determine whether antibiotic-induced dysbiosis (AID) is associated with alterations in dendritic morphology of GABAergic inhibitory interneurons in the medial entorhinal cortex (mEC), somatosensory cortex (SSC), motor cortex (MC), and hippocampus (Hp).

A cohort of six-month-old GAD-67-EGFP transgenic mice was treated with an antibiotic cocktail for two weeks, resulting in gut dysbiosis as validated by collecting stool samples at baseline and after treatment, then using next-generation sequencing of 16S ribosomal RNA.

The results demonstrate that the proposed model effectively exhibited the defining features of gut dysbiosis, including a significant reduction in microbiome diversity, expansion of pathobionts, and loss of beneficial microbes. The AID group showed alterations in density and morphology of GABAergic interneurons in different brain areas. The mean dendritic length and mean dendritic segments of the SSC and Hp were found to be significantly decreased, while no such decrease was observed in the mEC or MC. Furthermore, the density of interneurons was decreased in the mEC, Hp, and SSC areas, while no change was observed in the MC area.

The interneuron dysfunction plays a role in the pathogenesis of neurological disease. The findings of this study suggest that AID potentially influences the density and morphology of the interneurons, which may contribute to the development of neurological disorders.