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[Display omitted] • Constipation was associated with an increased risk of Alzheimer's disease (AD) in the South Korean cohort (discovery cohort, HR, 2.04; 95% CI, 2.01–2.07) and the Japan cohort (validation cohort, HR, 2.82; 95% CI, 2.61–3.05). • Loperamide-treated AD mouse model showed increased amyloid-beta and microglia in the brain with slow gut transit. • Loperamide-treated AD mouse model had increased transcription of genes related to norepinephrine secretion and immune responses and decreased transcription of defense against bacteria in colonic tissue. Although the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown. To investigate the potential association between slow gut transit and AD using epidemiological data and a murine model. We conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009–2010) and the follow-up period (2011–2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests. Constipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01–2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61–3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aβ and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue. Impaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted. [ABSTRACT FROM AUTHOR]

Objective: Migraine and irritable bowel syndrome (IBS) can be difficult-to-treat comorbidities that may be driven by underlying gut–brain axis dysfunction. This report describes utilization of a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet (LFD) in a patient with refractory migraine and co-occurring IBS. Methods: After unremarkable physical and neurological examinations, a 57-year-old woman with IBS and chronic migraine was started on a LFD under the guidance of a registered dietician. Psychometrically validated surveys administered at baseline and initial follow-up assessed patient-reported outcomes related to migraine and IBS symptoms. Results: At baseline, the patient reported 80/90 migraine days with average pain of 8/10, a Migraine Disability Assessment (MIDAS) score of 33, and Headache Impact Test-6 (HIT-6) score of 64, the latter 2 scores indicating severe disability. Baseline IBS symptom severity was noted at 9/10. Within 1 week on a LFD, the patient’s IBS symptoms and migraines improved in both frequency and intensity of episodes. After 5 weeks on a LFD elimination, the patient’s clinical improvement continued and she reported significant reduction in migraines, with average pain of 1/10 and IBS severity of 3/10. The patient also improved from severe to minimal levels of disability on validated measures (MIDAS, HIT-6, and IBS Patient Global Impression of Change). Conclusion: This is the first case report detailing successful initial treatment of migraine and co-occurring IBS utilizing a dietician-guided LFD. There are a number of important reasons for potential improvement in these gut–brain axis disorders which are reviewed as well as an implication for long-term management and food reintroduction. Larger, randomized trials evaluating a LFD in diverse individuals with migraine and co-occurring IBS are warranted to help confirm these results. [ABSTRACT FROM AUTHOR]

Cribbing is an oral stereotypic behavior in horses. Cribbing behavior (CB) has been associated with gastrointestinal (GI) dysfunction and gastric ulceration. This randomized crossover study aimed to evaluate the hypotheses that there would be differences in GI microbiota between horses receiving a gastric health support supplement or a placebo, as well as differences between cribbing horses (CBH) and noncribbing horses (NCBH). Mature Quarter Horses with CB (n = 4) and sex-matched noncribbing controls (NCB; n = 4) were randomly assigned to receive either a GI support supplement (TRT) or a placebo for 21 days, followed by a 2-week washout period. Treatment groups were then switched, and horses were treated for an additional 21 days. Before and after each treatment period, feces and gastric fluid samples were collected for microbiome analysis. Horses were acclimated for 2 weeks before the start of the study, individually stalled for 16 h/d, fed bermudagrass hay (1.2% body weight [BW], dry matter [DM] basis), and concentrated (0.5% BW), and turned out in pairs in paddocks for 8 h/d throughout the study. Fecal microbiota differed between CBH and NCBH (P = 0.001), although microbiota remained unaffected by TRT. No differences were found in the gastric microbiota between CBH and NCBH or between TRT and placebo. Administration of the supplement did not alter the GI environment of NCBH or CBH; however, a link between cribbing and fecal microbiota was found, suggesting that CBH may have a disrupted gut microbiome. • Fecal microbiota of cribbing horses differs from that of non-cribbing horses. • Cribbing horses showed a greater abundance of pathogenic bacteria. • No differences in gut microbiota between horses on GI supplement or placebo. • No differences in gastric microbiota between cribbing and non-cribbing horses. • The gastrointestinal support supplement did not affect cribbing rate. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that gut microbiota can affect the development of Alzheimer’s disease (AD) through various mechanisms. Bile acids (BAs), which are the final byproducts of cholesterol metabolism created through both the human body and gut microbiome, appear to be influenced by gut microbiota and may impact AD pathological characteristics such as the accumulation of tau and amyloid-β. We aimed to investigate the associations between various serum BAs and CSF biomarkers (including Aβ, total tau, and p-tau). Additionally, we sought to examine the longitudinal changes in brain Aβ and tau through PET imaging in relation to BAs profile. Methods: The data of 828 subjects including 491 diagnosed with mild cognitive impairment (MCI), 119 patients diagnosed with AD, and 267 cognitively normal (CN) participants were obtained from ADNI. The baseline and longitudinal [18F] florbetapir and [18F] flortaucipir PET standard uptake value ratios (SUVR) measures were obtained to assess the accumulation of tau and Aβ. Moreover, baseline levels of serum BAs and CSF Aβ1–42, tau, and p-tau were used. Results: After FDR correction we observed that five BAs level and relevant calculated ratios were associated with CSF p-tau and tau, three with CSF Aβ1–42. Furthermore, three BAs level and relevant calculated ratios were associated with the tau-PET rate of change, and two with the Aβ rate of change. Conclusion: The findings from our study suggest a correlation between altered profiles of BAs and CSF and imaging biomarkers associated with AD. These results provide supporting evidence for the link between the gut microbiome and the pathological features of AD. [ABSTRACT FROM AUTHOR]

Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. Abdominal migraine in childhood and adolescence may continue with migraine headaches in adulthood. This disease is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. It was shown that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs and associated mood disorders. Changes in the KYN pathway were shown in migraine and therefore it may be involved in AM pathogenesis. Abdominal migraine reflects an impairment in the communication within the gut-brain axis. Treatment approaches in AM are based on the experience of physicians, presenting personal rather than evidence-based practice, including efficacy of some drugs in adult migraine. Non-pharmacological treatment of AM is aimed at preventing or ameliorating AM triggers and is based on the STRESS mnemonic. Metabolic treatments with riboflavin and coenzyme Q10 were effective in several cases of pediatric migraine, but in general, results on metabolic treatment in migraine in children are scarce and nonconclusive. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Obese children show a higher headache prevalence and may be especially predisposed to AM, and KYN metabolites showed an alternated distribution in obese individuals as compared with their normal-weight counterparts. In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM, especially those with coexisting obesity. Further preclinical studies are needed to establish details of these trials. • Abdominal migraine links migraine and functional gastrointestinal diseases. • Tryptophan metabolism plays a role in migraine pathogenesis. • Metabolic treatment is especially suited for children. • Dietary interventions changing tryptophan content are justified in abdominal migraine. [ABSTRACT FROM AUTHOR]

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1 −/−) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy. Gut microbiota involved in Meth-induced colonic inflammation and depression- and anxiety-like behaviors, while SCFAs optimized gut homeostasis and ameliorated mental disorders by modulating the SIGMAR1/BDNF/TRKB pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression. [ABSTRACT FROM AUTHOR]

[Display omitted] • The crosstalk between the gut and the brain serves as a route for the spread of PD pathology in a bottom-up or top-down manner. • Gut dysbiosis is evident in PD patients and animal models and is associated with alterations in gut-derived microbial products and immune pathways promoting disease pathology. • Diet induces changes in the GM, with western diet evoking and Mediterranean diet preventing neuroinflammation and neurodegeneration associated with PD. • Gut-derived microbial products can be involved in the regulation of the immune system, the inflammation of both the intestine and the brain, and the integrity of intestinal epithelium and blood–brain barrier (BBB). • Therapeutic strategies that function by reversing gut dysbiosis and mitochondrial dysfunction may prove beneficial to treat PD pathology. Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved in neuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further explored in humans through clinical trials. Key Scientific Concepts of Review : Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD. [ABSTRACT FROM AUTHOR]

The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and lack of ability to process the data. In this review, we focused on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, and discussed the role of short-chain fatty acids and other important gut microbiome–derived metabolites. Of particular note is the action of gut microbiome–derived metabolites throughout the body, which impact processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system, but that are now recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlighted the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and reintroduces them. Taken together, study of the metabolites derived from the gut microbiome provided insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of, or involving, the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

The beneficial effects of probiotic consumption on age-related decline in cerebral function have been previously reported in the literature; however, the mechanistic link between gut and brain interactions has not yet been fully elucidated. Therefore, this study aimed to identify the role of gut microbiota-derived metabolites in gut-brain interactions via blood metabolomic profiling analysis in clinical trials and in vitro mechanistic studies. A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted in 63 healthy elderly individuals (≥65 years of age). Participants were administered either placebo (placebo group, N = 31) or probiotic capsules (Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI; probiotics group, N = 32) for 12 weeks. Global and targeted metabolomic profiling analyses of their blood samples were then performed using 1H nuclear magnetic resonance and liquid chromatography-mass spectrometry methods, both at baseline and at the end of the trial. Gut microbial analysis was conducted using the 16S ribosomal ribonucleic acid gene sequencing method. Subsequently, microglial BV2 cells were treated in vitro with indole-3-propionic acid (IPA) following lipopolysaccharide stimulation, and neuronal SH-SY5Y cells were treated with conditioned media from the BV2 cells. Finally, the levels of pro-inflammatory cytokines in BV2 cells and neurotrophins in SH-SY5Y cells were quantified using a real-time polymerase chain reaction or enzyme-linked immunosorbent assay. The metabolomic profiling analyses showed that probiotic consumption significantly altered the levels of metabolites involved in tryptophan metabolism (P < 0.01). Among these metabolites, gut microbiota-produced IPA had a 1.91-fold increase in the probiotics group (P < 0.05) and showed a significant relation to gut bacterial profiles (P < 0.01). Elevated IPA levels were also positively associated with the level of serum brain-derived neurotropic factor (BDNF) in the probiotics group (r = 0.28, P < 0.05), showing an inverse trend compared to the placebo group. In addition, in vitro treatment with IPA (5 μM) significantly reduced the concentration of proinflammatory TNF-α in activated microglia (P < 0.05), and neuronal cells cultured with conditioned media from IPA-treated microglia showed a significant increase in BDNF and nerve growth factor production (P < 0.05). These results show that gut microbiota-produced IPA plays a role in protecting the microglia from inflammation, thus promoting neuronal function. Therefore, this suggests that IPA is a significant mediator linking the interaction between the gut and the brain in the elderly with probiotic supplementation. [ABSTRACT FROM AUTHOR]

• Probiotic supplementation enhances cognitive functions in MCI older adults. • Probiotic supplementation benefits sleep quality in MCI older adults. • Probiotic supplementation increases the abundance of intestinal flora. Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI. [ABSTRACT FROM AUTHOR]

The aim of this systematic review was to determine: (1) differences between patients with AN and healthy controls (HC) in terms of gut microbiota community and intestinal barrier-related markers; (2) relationship between the intestinal ecosystem and health-related factors in AN individuals. We conducted a systematic literature search (PubMed, Embase, Clinical-Trials registry) until 30 September 2020 for studies reporting gut microbiome and intestinal barrier-related markers in patients with AN. Six studies on intestinal microbiota were eligible for this review, including three papers also describing intestinal barrier markers. Among five studies analyzing microbiota diversity, four of them found differences between AN patients and healthy controls (HC). The studies confirm alterations of the markers of the intestinal barrier integrity in patients with anorexia. The systematic review confirms changes in the gut ecosystem of patients with eating disorder, without a clear consensus of microbiota patterns in AN. Damage of intestinal barrier integrity is poorly documented in AN patients and needs more attention in further studies. [ABSTRACT FROM AUTHOR]

Neuropathology studies have shown that the pathognomonic feature of Parkinson's disease (PD), one of the most common neurodegenerative disorders, may start from the gut enteric nervous system and then spread to the central dopaminergic neurons through the gut–brain axis. With the advent of metagenomic sequencing and metabolomic analysis, a plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared with unaffected controls. Currently, although dopaminergic treatments and deep brain stimulation can provide some symptomatic benefits for motor symptoms of the disease, their long-term use is problematic. A mechanism-targeted therapy to halt the neurodegeneration is lacking. The recently observed gut microenvironmental changes in the early stages of the disease play a vital role in the PD pathogenesis. Patients whose disease begins in the gut may benefit most from interventions that target the gut microenvironments. In this review, we will summarize the current studies demonstrating multifunctional roles of gut microbiota in the gut–brain axis of PD and the currently available evidence for targeting the gut microbiota as a novel approach to potential disease-modifying therapy in PD. [ABSTRACT FROM AUTHOR]

• Short-chain fatty acids especially Butyrate can increase resilience in stress conditions. • Faecalibacterium prausnitzii is a kind of butyrate producing probiotic. • As a hypothesis, the composition of probiotics can be engineered to yield more butyrate. • As a hypothesis, in stress conditions, engineered Faecalibacterium prausnitzii can produce much butyrate. Social stress (SS) can lead to mental disorders (MD) in some people, such as depression and anxiety, while others who are resilient can handle SS without showing signs of mental illness. Resilience is characterized by human capacity to adapt to life's adverse events without losing function or developing a mental disorder. Exploring molecular processes can help elucidate resilience mechanisms that counteract the pathophysiology of depression. Gut microbiome plays an essential role in the homeostasis of human body, especially the central nervous system (CNS). Therefore, it may support the counterbalance of certain disorders, such as depression, through the microbiota-gut-brain (MGB) axis. Short-chain fatty acids (SCFAs) produced by the gut microbiota, such as butyrate, increase the transmission activity of neurotransmitters, brain-derived neurotrophic factor (BDNF) expression and the regulation of microglia maturation enhances resilience in response to stress. Probiotics can be engineered to yield more butyrate. However, the overproduction of SCFAs is not necessarily beneficial and may lead to known side effects, such as intestinal dysbiosis or metabolic dysfunction. Herein, as we hypothesized the potential effect of the microbiome in resilience promotion, we have designed a cortisol-sensitive operon that allows gut microbiota to regulate the production of SCFAs according to the environmental demands which produces butyrate only when responding to stress. Amongst gut bacteria, Faecalibacterium prausnitzii (F. prausnitzii) has large amounts of butyrate and can be manipulated by designed plasmid, a process which makes it a suitable candidate to be translated into clinic. [ABSTRACT FROM AUTHOR]

• LGZG decoction could ameliorate cognitive impairment in an AD-like mouse model. • LGZG decoction could remodel the intestinal microecology, particularly SCFAs-generated bacteria, such as augment the levels of Bacteroidetes and the ratio of Firmicutes to Bacteroidetes. • LGZG decoction could enhance the integrity of the intestinal and brain tissue barriers, and modulate aβ transportation through gut microbiota metabolite SCFAs. • The neuroprotective effect of SCFAs on the AD-like mouse model may be regulated through the inhibition of pP38 of the MAPK signaling pathway. Lingguizhugan (LGZG) decoction, an ancient Chinese herbal remedy originating from the Eastern Han Dynasty, consists of Poria cocos, Cinnamomi ramulus, Atractylodes macrocephala , and Glycyrrhiza , as described in the Golden Chamber Synopsis. It has a history spanning over 1600 years, in which it has been primarily used for the treatment of inflammation, injuries, and fluid retention; however, the potential of LGZG decoction to ameliorate Alzheimer's disease (AD) progression by modulating the gut–brain axis through attenuation of gut microbiota and their metabolites remains unknown. To examine the in vivo anti-AD effects and mechanism of LGZG decoction in alleviating AD cognitive impairment. Two-part experiments in vivo were designed, one for behavior tests, intestinal and brain histopathology, intestinal microbiome and quantitative determination, and another one for metabolite supplementation study. AlCl 3 /D-gal was used to establish an AD-like mouse model. Behavioral tests, such as the Morris water maze test, were used to assess the effect of LGZG decoction on cognitive dysfunction. The concentration of proinflammatory mediators was measured by ELISA. The protein content was detected by western blot analysis and immunohistochemistry. The content of short-chain fatty acids was measured by LC-MS/MS. Evaluation of 16S rRNA gene sequencing for species and strain-level gut microbiome analysis was performed. LGZG decoction mitigated cognitive impairment in an AD-like mouse model, and decreased the deposition of amyloid-β and the production of proinflammatory cytokines in the brain. LGZG decoction remodeled the intestinal microecology, enhanced the integrity of the intestinal and brain tissue barriers, and modulated Aβ transportation through gut microbiota metabolite SCFAs. The neuroprotective effect of SCFAs on the AD-like model mice may be manifested through the inhibition of pP38 of the MAPK signaling pathway. Our results suggest that LGZG decoction reshapes the gut microbiota. SCFAs derived from the gut microbiota ameliorate the cognitive decline induced by AlCl 3 /D-gal through the gut–brain axis and reduce brain Aβ aggregation. We propose LGZG decoction as a potential therapeutic option for AD. [Display omitted] [ABSTRACT FROM AUTHOR]

Pelvic health physical therapy's primary role in gastroenterology-related care has been primarily viewed as biofeedback therapy of the pelvic floor muscles in the medical literature; however, emerging research suggests that expanding this role toward a whole-body approach may be optimal. Common gastroenterology-related referrals to pelvic health physical therapy include chronic constipation, fecal incontinence, levator ani syndrome, and mixed presentations of those mentioned previously. Many of these common referral diagnoses fall under the umbrella of disorders of gut-brain interaction (DGBIs) and have associated impairments involving multiple bodily systems. Pelvic health physical therapists have a robust knowledge of multiple bodily systems and are well-positioned providers for individuals with DGBIs as part of an interdisciplinary team and can incorporate an expanded plan of care outside of direct pelvic floor muscle interventions for best practice. Additional components of a plan of care for individuals with DGBIs that the following article reviews include the incorporation of physical activity and targeting cardiopulmonary measures, mental health considerations, and nutrition-based advice. [ABSTRACT FROM AUTHOR]

The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the enteric nervous system. This interplay provides a link between exogenous environmental stimuli such as nutrient sensing, and nervous system function, as well as a mechanism of feedback from cortical and sensory centers of the brain to enteric activities. The intestinal epithelium is one of the human body's largest sources of hormones and neurotransmitters, which have critical effects on neuronal function. The influence of the gut microbiota on these processes appears to be profound; yet to date, it has been insufficiently explored. Disruption of the intestinal microbiota is linked not only to diseases in the gut but also to brain symptomatology, including neurodegenerative and behavioral disorders (Parkinson disease, Alzheimer disease, autism, and anxiety and/or depression). In this review we discuss the cellular wiring of the gut-brain axis, with a particular focus on the epithelial and neuronal interaction, the evidence that has led to our current understanding of the intestinal role in neurologic function, and future directions of research to unravel this important interaction in both health and allergic disease. [ABSTRACT FROM AUTHOR]

Neueste wissenschaftlichen Erkenntnisse über das vegetative Nervensystem werfen unser Denkmodell der Anatomie über den Haufen. Aktuelle Studien zeigen, dass es anscheinend keine parasympathischen Nervenfasern im sakralen Rückenmark gibt. Zudem zählen, neben Sympathikus und Parasympathikus, noch zwei weitere Strukturen zum vegetativen Nervensystem – das enterische Nervensystem und das „little brain on the heart". Die klinischen Krankheitsbilder der vegetativen Nervensysteme sind längst Gegenstand der osteopathischen Forschung und lassen sich anscheinend positiv beeinflussen. The latest scientific findings about the autonomic nervous system throw our way of thinking about anatomy upside down. Recent studies show that there appear to be no parasympathetic nerve fibers in the sakral spinal cord. In addition to the sympathetic and parasympathetic nervous system, there are two other structures in the autonomic nervous system – the enteric nervous system and the „little brain on the heart". The clinical symptoms of the vegetative nervous system have long been a subject of osteopathic research and can be positively influenced. [ABSTRACT FROM AUTHOR]

Introduction: For years, tinnitus has become a prevalent symptom in the ENT department. However, the mechanism underlying tinnitus remains unclear. There is increasing evidence that tinnitus is related to an abnormal central gain in the central auditory system and increased neuroinflammatory mediators. On the other hand, recent studies have shown that gut dysbiosis plays a crucial role in brain function, and gut dysbiosis contributes to several neurological diseases. Hence, giving insight into its possible involvement in tinnitus. Aims: This study evaluated the potential role of gut microbiota dysbiosis in the path mechanism of tinnitus, mainly through its effect on neurotransmitter production and neuroinflammation induction. Methods: This study uses a literature review approach, inclusive only of experimental studies in the recent five years discussing gut dysbiosis, neurotransmitter, neuroinflammation, and tinnitus signaling. Results: From 22 relevant literature, we found that gut dysbiosis impacts neurotransmitter production such as GABA and 5-HT and contributes to the neuroinflammatory process by increasing pro-inflammatory cytokines and activated microglia. These altered neurotransmitter profiles and triggered pro-inflammatory mediators were also found in tinnitus. Conclusion: Gut microbiota dysbiosis is likely to underlie tinnitus's pathomechanism by altering neurotransmitter production and activating the neuroinflammatory response in the brain. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metabolomics allow for the output of nutritional supplements to be measured after they are utilized by the gut microbiome. • After digestion, portions of nutritional supplements make it to the gut microbiota and are subsequently metabolized. • AG1 supplementation led to a change in 57 polar metabolites during colonic fermentation by ex vivo human gut microbiota. • Clinical investigation must be done to confirm the presence of these metabolites and measure the beneficial health outcomes. Metabolomics is a critical approach to fully understand the metabolic repercussions of a nutritional supplement on the gut microbiota. Here, a proof of principle study was conducted via a metabolomic survey of polar metabolites to explore the effect of AG1 on the metabolic output of the human gut microbiota, in vitro , using the Simulator of the Human Intestinal Microbial Ecosystem® (SHIME). Aliquots were isolated from the fecal slurry at baseline (0 h), 1 h, 24 h, and 48 h of colonic fermentation simulation. Chemical analysis at these timepoints detected a total of 165 metabolites with 57, 21, and 14 specific metabolites being significantly altered by AG1 relative to the blank controls at 1 h, 24 h, and 48 h, respectively. Many of these metabolites likely resulted from AG1 directly as a supplement, but several of these metabolites also likely arose specifically from microbial metabolism. [ABSTRACT FROM AUTHOR]

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth. [Display omitted] • Gestational diabetes mellitus (GDM) mothers have distinct gut microbiomes during pregnancy • GDM fingerprints on the offspring's gut microbiome are confounded by C-section • GDM affects the offspring's head circumference growth in a sex-dependent manner • The gut microbiome of GDM mothers with male fetuses has different gut-brain modules Gestational diabetes mellitus (GDM), defined as hyperglycemia during pregnancy, is the leading gestational complication worldwide. Assessing the fecal microbiome in 264 mother-baby pairs, Wang et al. demonstrate that GDM affects both maternal and infant gut microbiome composition and gut-brain modules, which are associated with infant head growth in sexual dimorphism. [ABSTRACT FROM AUTHOR]

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions. • The gut microbiota shapes the CNS through the intricate gut-brain axis network. • Gut microbiota influences mental health via neurotransmitter modulation, neuroinflammation and gut barrier integrity. • Gut microbiota dysbiosis contributes to neuropsychiatric disorders like anxiety, depression, and bipolar disorders. • The research underscores probiotics/prebiotics in alleviating mental illness symptoms. [ABSTRACT FROM AUTHOR]

As prebiotics, plant-origin polysaccharides can be metabolized by the gut microbiota, leading to the production of metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters. Probiotics, and their metabolites, help balance both anti-inflammatory and pro-inflammatory responses through various mechanisms. Moreover, probiotics can metabolize prebiotics into neurotransmitters which influence the brain-gut axis, thereby reducing anxiety and stress. There exists a synergistic effect between prebiotics and probiotics in maintaining gut homeostasis via the microbiota-gut-brain axis. For improvisation of the oral transfer mode of probiotics delivery within the intestine along with viability, efficacy, and stability co-encapsulation is required. Personalized nutrition and precision medicine are beginning to shape the application of both probiotics and prebiotics, with a growing interest in understanding the microbial characteristics associated with health and disease. This review aims to summarize the sources, types, and structures of plant polysaccharides. The co-encapsulation systems involving prebiotics and probiotics present potential applications in modulating gut homeostasis and the brain-gut axis in future. [Display omitted] • Plant-origin polysaccharides as prebiotics can modulate gut microbiota composition. • Probiotics can improve the balance of the gut microbiota and stimulate the immune system. • The microencapsulated delivery system improves the survival of probiotics in the intestine. • Prebiotics and probiotics can exert a synergistic effect on modulating gut homeostasis and the brain-gut axis. [ABSTRACT FROM AUTHOR]

• ASD is a multifactorial neurodevelopmental disorder. • The gut microbiota is significant in the formation and onset of ASD. • Gut and brain have a bi-directional communication. • This review discusses about gut microbiota, its metabolites and its role in ASD. Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue. [ABSTRACT FROM AUTHOR]

This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT. The Rome Foundation's Working Team Report on Brain-Gut Behavior Therapies empowers gastroenterologists to effectively communicate the scientific rationale for and the approach to brain-gut behavior therapies as part of integrated care. [ABSTRACT FROM AUTHOR]

Peanuts are rich in bioactive compounds that may have a positive impact on memory and stress response. To evaluate the effect of regular consumption of peanut products on cognitive functions and stress response in healthy young adults. A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults that consumed 25 g/day of skin roasted peanuts (SRP, n = 21), 32 g/d of peanut butter (PB, n = 23) or 32 g/d of a control butter made from peanut oil (free of phenolic compounds and fiber) (CB, n = 19) for six months. Polyphenol intake, cognitive functions, and anxiety and depression scores were evaluated using validated tests. Fecal short-chain fatty acids (SCFAs) and plasma and fecal fatty acids were assessed by chromatographic methods. Urinary cortisol was quantified by an enzymatic method. Comparing the two interventions with the control, a significant reduction in anxiety scores was observed in the SRP compared to the CB group. After the intervention, consumers of SRP and PB had an improved immediate memory (p = 0.046 and p = 0.011). Lower anxiety scores were associated with SRP and PB (p < 0.001 and p = 0.002, respectively) and lower depression scores with SRP, PB and CB (p = 0.007, p = 0.003 and p = 0.032, respectively). Memory functions and stress response were significantly correlated with polyphenol intake, fecal SCFAs, plasma and fecal very long chain saturated fatty acids (VLCSFAs). Regular peanut and peanut butter consumption may enhance memory function and stress response in a healthy young population. These effects seem to be associated with the intake of peanut polyphenols, increased levels of fecal SCFAs, and unexpectedly, VLCSFAs, which were also present in the control product. [ABSTRACT FROM AUTHOR]

This review aims to understand and analyse the effects of probiotics on depression, anxiety and psychological stress. These disorders are among the leading causes of disability worldwide. Conventional pharmacotherapies usually have a poor response or adverse side effects. In this context, recent studies have demonstrated a dense bi-directional communication named gut-brain axis. Evidences are demonstrating the relationship between disturbance in the enteric microbiome and psychiatric disorders, paving the way for the emergence of alternative therapies. A systematic search for randomized double/triple blind placebo-controlled clinical trials was performed in PubMed, Scopus and Lilacs. The studies selection followed the recommendations of the main items for report systematic reviews and meta-analyses (PRISMA). Nine articles met the criteria and were analysed for effects on depression, anxiety, psychological stress and biomarkers. Seven found positive results in at least one of the items. We concluded that the use of probiotics to alleviate depressive symptoms and anxiety is promising, mainly due to its potential anti-inflammatory effect, but additional and more rigorous double blind randomized clinical trials are necessary to endorse such conclusions. [ABSTRACT FROM AUTHOR]

This paper analyses computationally the effect of the gut microbiome on social interaction deficits related to ASD. An integrative second-order adaptive network model is introduced that integrates the relevant mental and physiological causal pathways and their (second-order) adaptivity. [ABSTRACT FROM AUTHOR]

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The gut-brain axis is a crucial interface between the central nervous system and the gut microbiota. Recent evidence shows that exposure to environmental contaminants, such as heavy metals, can cause dysbiosis in gut microbiota, which may affect the gut-brain communication, impacting aspects of brain function and behavior. This systematic review of the literature aims to evaluate whether deleterious effects on brain function due to heavy metal exposure could be mediated by changes in the gut microbiota profile. Animal studies involving exposure to heavy metals and a comparison with a control group that evaluated neuropsychological outcomes and/or molecular outcomes along with the analysis of microbiota composition were reviewed. The authors independently assessed studies for inclusion, extracted data and assessed risk of bias using the protocol of Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) for preclinical studies. A search in 3 databases yielded 16 eligible studies focused on lead (n = 10), cadmium (n = 1), mercury (n = 3), manganese (n = 1), and combined exposure of lead and manganese (n = 1). The animal species were rats (n = 7), mice (n = 4), zebrafish (n = 3), carp (n = 1) and fruit fly (n = 1). Heavy metals were found to adversely affect cognitive function, behavior, and neuronal morphology. Moreover, heavy metal exposure was associated with changes in the abundance of specific bacterial phyla, such as Firmicutes and Proteobacteria , which play crucial roles in gut health. In some studies, these alterations were correlated with learning and memory impairments and mood disorders. The interplay of heavy metals, gut microbiota, and brain suggests that heavy metals can induce direct brain alterations and indirect effects through the microbiota, contributing to neurotoxicity and the development of neuropsychological disorders. However, the small number of papers under review makes it difficult to draw definitive conclusions. Further research is warranted to unravel the underlying mechanisms and evaluate the translational implications for human health. [Display omitted] • This systematic review included 16 studies that exposed animals to Pb, Mn, Cd and Hg. • Heavy metal exposure affects gut microbiota, cognition, behavior & brain morphology. • Majors changes were in Firmicutes and Proteobacteria, albeit with conflicting results. • Gut dysbiosis due to heavy metals were correlated with mood and cognitive disorders. • Further research is essential to uncover mechanisms and health implications. [ABSTRACT FROM AUTHOR]

The gut-brain axis (GBA) plays a central role in cerebral ischaemia-reperfusion injury (CIRI). Rhubarb, known for its purgative properties, has demonstrated protective effects against CIRI. However, it remains unclear whether this protective effect is achieved through the regulation of the GBA. This study aims to investigate the mechanism by which rhubarb extract improves CIRI by modulating the GBA pathway. We identified the active components of rhubarb extract using LC-MS/MS. The model of middle cerebral artery occlusion (MCAO) was established to evaluate the effect of rhubarb extract. We conducted 16S rDNA sequencing and untargeted metabolomics to analyze intestinal contents. Additionally, we employed HE staining, TUNEL staining, western blot, and ELISA to assess intestinal barrier integrity. We measured the levels of inflammatory cytokines in serum via ELISA. We also examined blood-brain barrier (BBB) integrity using Evans blue (EB) penetration, transmission electron microscopy (TEM), western blot, and ELISA. Neurological function scores and TTC staining were utilized to evaluate neurological outcomes. We identified twenty-six active components in rhubarb. Rhubarb extract enhanced α-diversity, reduced the abundance of Enterobacteriaceae, and partially rectified metabolic disorders in CIRI rats. It also ameliorated pathological changes, increased the expressions of ZO-1, Occludin, and Claudin 1 in the colon, and reduced levels of LPS and d -lac in serum. Furthermore, it lowered the levels of IL-1β, IL-6, IL-10, IL-17, and TNF-α in serum. Rhubarb extract mitigated BBB dysfunction, as evidenced by reduced EB penetration and improved hippocampal microstructure. It upregulated the expressions of ZO-1, Occludin, Claudin 1, while downregulating the expressions of TLR4, MyD88, and NF-κB. Similarly, rhubarb extract decreased the levels of IL-1β, IL-6, and TNF-α in the hippocampus. Ultimately, it reduced neurological function scores and cerebral infarct volume. Rhubarb effectively treats CIRI, potentially by inhibiting harmful bacteria, correcting metabolic disorders, repairing intestinal barrier function, alleviating BBB dysfunction, and ultimately improving neurological outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and demyelination of neurons. There is evidence to suggest that level of a neurotransmitter gamma-aminobutyric acid (GABA), due to the degradation by γ-aminobutyric acid transaminase (GABAT), is reduced in certain areas of the brain in MS patients. MS is always accompanied by gut bacteria dysbiosis. In healthy individuals, Faecalibacterium sp. while in MS patients A. calcoaceticus, Clostridium sp. and S. typhimurium are found abundantly. Although all these microbes produce GABAT but only in MS patients this enzyme significantly degrades GABA. Present study is an attempt to characterize the GABAT protein sequences of these bacteria. Sequences of GABAT protein were retrieved from Uniprot database. Sequences were analyzed by Protparam, Gneg-mPLoc, SOSUI, PFP-FunDSeqE, Pepwheel program, PROTEUS and Alphafold and SAVES servers, MEME suite and HDOCK server. In healthy individuals gastrointestinal tract (GIT) bacteria, GABAT protein was present in inner-membrane with α helix content (61 and 62%) and β sheet content (5%), 4-helical cytokines functional domains. It has greater number of B-cell epitopes and more complex 3D configuration as compared to MS patients GIT bacterial enzymes. Present study might enable us to modify the GABAT encoding gene and enzyme through site-directed mutagenesis in pathogenic bacteria thus reducing their potential of causing MS. [ABSTRACT FROM AUTHOR]

The brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal Lactobacillus murinus , increasing the production of indole-3-acetate (IAA), which contributes to a transferrable loss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergetics and thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oral α-ketoglutarate supplementation bolsters ISC differentiation and confers resilience to stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higher in patients with mental distress and is correlated with gut dysfunction. These findings uncover a microbe-mediated brain-gut pathway that could be therapeutically targeted for stress-driven gut-brain comorbidities. [Display omitted] • Psychological stress shapes ISC fate decision via gut microbial remodeling • Microbial IAA acts on ISC mitochondria to impede secretory cell lineage commitment • Supplementation of α-ketoglutarate rescues both IAA and stress-induced ISC defect • IAA production is increased in the gut of patients with mental stress The mechanism by which psychological stress disturbs gut homeostasis remains incompletely understood. Wei et al. report that stress enriches gut commensal Lactobacillus murinus and the production of indole-3-acetate, which contributes to a transferrable impairment of secretory cell differentiation in mice via disturbing mitochondrial respiration of intestinal stem cells. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic mental disorder with marked symptoms of hallucination, delusion, and impaired cognitive behaviors. Although multidimensional factors have been associated with the development of schizophrenia, the principal cause of the disorder remains debatable. Microbiome involvement in the etiology of schizophrenia has been widely researched due to the advancement in sequencing technologies. This review describes the contribution of the gut microbiome in the development of schizophrenia that is facilitated by the gut-brain axis. The gut microbiota is connected to the gut-brain axis via several pathways and mechanisms, that are discussed in this review. The role of the oral microbiota, probiotics and prebiotics in shaping the gut microbiota are also highlighted. Lastly, future perspectives for microbiome research in schizophrenia are addressed. [ABSTRACT FROM AUTHOR]

Research increasingly demonstrates the bidirectional communication between gut microbiota and the brain, enhancing the role of gut microbiota modulation in the treatment of central nervous system (CNS) disorders. The first five years of life are extremely important as it affects the development of gut microbiota, immune system and, consequently, the onset of psychometric alterations, particularly in genetically predisposed individuals. In this review, we focus on the link between specific microbial genera, gastrointestinal (GI) disorders, anxiety and depression and on the effects of different therapeutic strategies for mood disorders on gut microbiota. [ABSTRACT FROM AUTHOR]

Anxiety and stress can trigger functional gastrointestinal disorders, whereas gastrointestinal symptoms can significantly increase anxiety and depression levels. These patterns are associated with the connection of the intestine and the brain through the "gut-brain axis," a bi-directional communication of the nervous, endocrine, and immune systems. This clinical trial sought to investigate the effects of a novel nutraceutical supplement (Relaxigen Pet dog) containing natural anti-inflammatory compounds (CLA, Krill), pre/probiotics, 5-HTP, and L-theanine on stress-related behavior and to assess the connection between these stress-related behaviors and the fecal microbiome in dogs. Forty dogs, ranging in ages from 1 to 10 years, took part in this double-blind, placebo-controlled clinical trial. Ten dogs were control dogs without overt clinical signs of anxiety. Thirty dogs (experimental dogs) with signs of stress and anxiety were randomly assigned to the treatment (N = 20) and placebo (N = 10) groups. The treatment sample group (20 dogs balanced for sex) was administered with Relaxigen Pet dog tablets and the placebo group (10 dogs balanced for sex) with placebo tablets by mouth once a day for 60 days. A basic history questionnaire that focused on all aspects of dog's behavior, management, health issues, and behavioral signs of stress and anxiety, was collected at days 0, 30, and 60 for each experimental dog. A fecal sample was collected for all dogs at day 0 to compare the microbiome of the anxious and non-anxious dogs. The anxious dogs in the treatment and placebo dogs groups had a fecal sample collected again at 30 and 60 days. These samples were used to extract the DNA for microbiological analysis and to determine the leading bacterial group. ANOVA showed an influence of treatment × time and the group that received the treatment had a probability of improving greater than 10% (P ≤ 0.05). This study revealed a different structure of the intestinal microbiota between healthy dogs and those with stress-related behaviors at baseline. Supplementation with the Relaxigen seems to bring some changes in bacterial groups concentration in the treatment group of anxious dogs compared to the placebo one, but we must be very cautious in presenting these results due to the limitations of this pilot study (number of subjects, no dietary control, and no evaluation of microbiota over time for the control group dogs). [ABSTRACT FROM AUTHOR]

Bariatric surgery is currently the most efficacious and durable intervention for severe obesity. The most commonly performed procedures in the United States are the Roux-en-Y gastric bypass and the sleeve gastrectomy, which involve significant anatomic and physiologic alterations that lead to changes in behavior and biology. Unfortunately, many patients experience suboptimal weight loss and/or substantial weight regain. Eating and physical activity/sedentary behaviors, mood, cognition, and the gut microbiome all change postoperatively and have an association with weight change. The longitudinal relationship between changes in the gut microbiome and postoperative weight trajectory has not been explored thoroughly, and the interactive associations among the gut microbiome and the other variables that impact weight have been similarly understudied. The following is a methods and design description for a prospective, 24-month longitudinal study of 144 bariatric surgery patients, at 2 sites, that aimed to identify predictors of weight loss trajectories over 24 months after Roux-en-Y gastric bypass and the sleeve gastrectomy. Specifically, the study will examine the relationships between empirically supported behavioral and biological variables and their combined impact on postoperative weight trajectories. Novel data collection will include intensive measurement of problematic eating behaviors and diet and physical activity postoperatively, which may be altered in parallel with, or in response to, changes observed in the gut microbiota. Identifying postoperative predictors of weight loss and co-morbidity resolution should inform development of novel interventions that are tailored to individual patients' risk profiles to optimize and sustain more favorable weight trajectories. • Suboptimal weight loss and weight regain following bariatric procedures affect a significant subset of patients. • Behavioral and psychological factors have been identified as risk factors. More recently the impact of gut microbiota have also been implicated. However, studies have not examined both of these in prospective trials. • The current trial employs novel data collection and may help inform development of novel interventions that that are tailored to individual patients' risk profiles to optimize and sustain more favorable weight trajectories. [ABSTRACT FROM AUTHOR]

With the occurrence of aging process, decreased neuron dopamine, disrupted brown adipose tissue (BAT) remodeling and decreased butyrate level all reflect a weak host healthy in certain degree. Nevertheless, the signs of mid-adult gut microbiota, and its association with host healthy are not well understood. In current study, we deemed to illustrate the associations of age, neuron dopamine, BAT remodeling, butyrate and gut microbiota with the aid of traditional herbal formula Kang Shuai Lao Pian (KSLP), which is known for its anti-aging effect. Here, ELISA was performed to detect the production of brain dopamine, the mass of inguinal white adipose tissue versus interscapular brown adipose tissue (iWAT/iBAT) was calculated and considered as a sign of BAT remodeling, 16S rRNA gene sequencing was used to the detection of gut microbiota profiling and gas chromatography was used to measure the butyrate level in mice feces. Our results indicated mid-adult mice already present distinctive gut microbiota profiling compared with young mice, concomitant with which are the lower brain dopamine level and disrupted brown adipose remodeling. KSLP treatment improved the host healthy and regulated gut microbiota with enriched Firmicutes at the expense of Bacteroidetes, particularly increased the relative abundance of bacteria functionally related to dopamine and butyrate productions, which suggest KSLP treatment constructs a healthier gut environment. In conclusion, modulation of gut microbiota and butyrate may connectively regulate dopamine production and BAT remodeling through gut-brain axis and gut-metabolism axis. [ABSTRACT FROM AUTHOR]

The modulation of the microbiota-gut-brain axis with a view to preventing and treating brain disorders became recently a hot topic for the scientific community. Dietary polyphenols are multifaceted compounds that have demonstrated to be highly advantageous to counteract inflammation, oxidative stress, and neurodegeneration, among other pathological conditions, being useful in the prevention and treatment of several chronic disorders. The potential of these compounds to prevent and treat brain disorders has not been only related to their capacity to reach the brain, depending on their chemical structure, and interact directly with brain cells, but also to their ability to modulate the communication between the brain and the gut, interfering with multiple branches of this axis. Preclinical studies have demonstrated the potential of these food bioactive compounds in brain diseases, namely, neurodevelopmental, such as Down's syndrome and Autism spectrum disorder, neurodegenerative, such as Parkinson's disease and Alzheimer's disease, and psychiatric disorders, such as depression and anxiety. Until now, dietary polyphenols have been recognized as promising nutraceuticals to combat brain disorders. However, the impact of these compounds on the gut-brain interconnection remains poorly elucidated. Also, clinical assays are crucial to further support the beneficial effects of these compounds as demonstrated in preclinical research. [ABSTRACT FROM AUTHOR]

Gene-environment interactions shape behavior and susceptibility to depression. However, little is known about the signaling pathways integrating genetic and environmental inputs to impact neurobehavioral outcomes. We report that gut G-protein-coupled receptor, Gpr35 , engages a microbe-to-brain metabolic pathway to modulate neuronal plasticity and depressive behavior in mice. Psychological stress decreases intestinal epithelial Gpr35 , genetic deletion of which induces depressive-like behavior in a microbiome-dependent manner. Gpr35 −/− mice and individuals with depression have increased Parabacteroides distasonis , and its colonization to wild-type mice induces depression. Gpr35 −/− and Parabacteroides distasonis -colonized mice show reduced indole-3-carboxaldehyde (IAld) and increased indole-3-lactate (ILA), which are produced from opposing branches along the bacterial catabolic pathway of tryptophan. IAld and ILA counteractively modulate neuroplasticity in the nucleus accumbens, a brain region linked to depression. IAld supplementation produces anti-depressant effects in mice with stress or gut epithelial Gpr35 deficiency. Together, these findings elucidate a gut microbe-brain signaling mechanism that underlies susceptibility to depression. [Display omitted] • Gut epithelial Gpr35 deficiency triggers depressive-like behaviors in mice • Colonization with P. distasonis , which is enriched in Gpr35 −/− mice, elicits depression • P. distasonis alters IAld and ILA balance, which regulates synaptic plasticity and depression • IAld supplementation alleviates depressive symptoms in Gpr35 −/− and stressed mice How host genetics interplay with environmental factors to shape depression remains largely unknown. Cheng et al. report that Gpr35 deficiency triggers depressive symptoms in mice due to microbiome alterations, specifically Parabacteroides distasonis. These changes are linked to diminishment of a bacterial metabolite indole-3-carboxaldehyde, affecting neuroplasticity in the nucleus accumbens. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effects relevant to the chronic complications of type 2 diabetes. Although GLP-1RAs attenuate T cell-mediated gut and systemic inflammation directly through the gut intraepithelial lymphocyte GLP-1R, how GLP-1RAs inhibit systemic inflammation in the absence of widespread immune expression of the GLP-1R remains uncertain. Here, we show that GLP-1R activation attenuates the induction of plasma tumor necrosis factor alpha (TNF-α) by multiple Toll-like receptor agonists. These actions are not mediated by hematopoietic or endothelial GLP-1Rs but require central neuronal GLP-1Rs. In a cecal slurry model of polymicrobial sepsis, GLP-1RAs similarly require neuronal GLP-1Rs to attenuate detrimental responses associated with sepsis, including sickness, hypothermia, systemic inflammation, and lung injury. Mechanistically, GLP-1R activation leads to reduced TNF-α via α 1 -adrenergic, δ-opioid, and κ-opioid receptor signaling. These data extend emerging concepts of brain-immune networks and posit a new gut-brain GLP-1R axis for suppression of peripheral inflammation. [Display omitted] • GLP-1R agonism attenuates TLR-induced inflammation • Semaglutide reduces the severity of polymicrobial inflammation • Anti-inflammatory actions of GLP-1R agonists require CNS GLP-1Rs • GLP-1R agonists reduce inflammation through CNS adrenergic and opioid GPCRs GLP-1R agonists may reduce cardiometabolic complications in part through reduction of inflammation. Here we show, using pharmacology and genetics, that the anti-inflammatory actions of GLP-1RAs to reduce TLR-mediated inflammation require CNS GLP-1R signaling. [ABSTRACT FROM AUTHOR]

[Display omitted] • Review delves into gut microbiome's role in Alzheimer's modulation. • Dysbiosis linked to neuroinflammation, amyloid beta aggregation, and oxidative stress. • Complex mechanisms involve microbial metabolites, immune signaling, permeability, and vagus nerve. • Probiotic exopolysaccharides protect neurons, inhibit amyloid beta, and improve memory in Alzheimer's models. The effects of the gut microbiome on the brain and the mechanisms of gut-brain communication have been popular research topics for the past few decades. The term gut-brain axis (GBA) evolved to illustrate how the gut and gut microbiota communicate with the brain. The gut-brain axis is an interplay of the neural, endocrine, immune, and metabolic pathways that help to maintain the brain's homeostasis. Several groups have reported that gut dysbiosis is significantly associated with neuroinflammation, aggregation of amyloid beta, and an increase in oxidative stress during Alzheimer's disease (AD). Understanding the exact mechanism of how the gut microbiome influences brain function may help develop new therapeutic modalities for AD. This review highlights the functioning of the gut microbiome in AD pathogenesis, the potential beneficial effects of probiotic exopolysaccharides as therapeutic molecules, and the potential benefits of probiotic exopolysaccharides (EPS) as a ray of hope in treating AD. [ABSTRACT FROM AUTHOR]

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli -mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli- mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis. [Display omitted] • Prenatal caffeine exposed-offspring develop ASD after a high-fat diet. • Microbiota-IL-17A-brain axis mediates high-fat diet-induced ASD in PCE offspring. • Escherichia coli is a major link in high-fat diet-induced ASD of PCE offspring. [ABSTRACT FROM AUTHOR]

Arsenic is a widely distributed ecotoxic pollutant that has been found to cause neurotoxicity in a variety of species. Gut-brain axis is a two-way information network between the gut microbiome and the brain, which is closely related to organismal health. However, the role of the gut-brain axis in arsenic-induced neurotoxicity remains largely unknown. In order to explore whether there is a relationship between brain and gut microbiota of meat ducks, we performed molecular biological detection including RT-qPCR and Western blot, as well as morphological detection including, HE staining and immunohistochemistry. Meanwhile, intestinal contents were analyzed using 16 S ribosomal RNA gene sequencing and analysis In this study, we investigated whether arsenic trioxide (ATO) can activate the gut microbiome-brain axis to induce intestinal and brain injury. The results showed that ATO-exposure disrupted the diversity balance of intestinal microbiota and integrity and injured the intestinal structure. ATO-exposure also reduced the number of glycogen and goblet cells in the duodenum. In addition, exposure to ATO caused intestinal inflammatory injury by activating NF-κB signaling pathway and promoting the expression of its target genes. Meanwhile, the tight junction-related proteins (ZO-1, occludin) of gut and brain were reduced by ATO exposure. Furthermore, results also revealed that ATO-exposure induced brain injury, including neuronal cell vacuolization and reduced numbers of neuronal cells in the cortex and hippocampus. Remarkably, ATO-exposure also disrupted neurotransmitter levels. Additionally, our further molecular mechanism study revealed that ATO-exposure increased the expression of autophagy and apoptosis related mRNA and proteins levels in the brain tissues. Altogether, these findings provide a new insight into that ATO-exposure induced intestinal injury and aggravated neurotoxicity via the gut-brain axis. [Display omitted] • ATO exposure disrupted the diversity of gut microbiota. • ATO exposure induced inflammatory reaction in duodenum of duck. • Autophagy and apoptosis were involved in ATO-induced neurotoxicity. • Mechanism of gut-brain axis provided a novel insight into the arsenic toxicity. [ABSTRACT FROM AUTHOR]

Social interaction difficulties and loneliness as well as activation of immunological pathways and a status of low-grade immune-inflammation are thought to be associated with psychotic disorders. So far, a single biomarker that indicates disordered social interaction as part of psychotic disorders and immune-inflammation has yet to found but could be clinically useful. If low-grade immune-inflammation is a contributor to psychotic disorders, it raises the question where exactly, when and why it begins to negatively impact the human body? Deviant gut microbiota have been discussed in this context. Here, stress resulting from disordered social interaction may contribute to the disruption of the intestinal barrier. Lipopolysaccharides (LPS) from bacteria can enter the body leading to an activation of monocytes – among others – via the cluster of differentiation 14 (CD14) and further influencing central nervous structures. CD14 can be released by monocytes upon activation as a soluble form (sCD14). We hypothesize that sCD14 could be a useful biomarker to evaluate the consequences of disordered social interaction in psychotic patients including low-grade immune-inflammation via the gut-brain axis. This could be performed using an analysis of gut microbiota, flow cytometry and proteome analysis of blood and cerebrospinal fluid (CSF) and cerebral Magnetic Resonance Imaging (MRI) together with further systematic evaluations of social behavior. [ABSTRACT FROM AUTHOR]