Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

Introduction: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. Methods: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. Results: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. Conclusion: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

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.

Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment.

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100ß, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

Current landscape of fecal microbiota transplantation in treating depression.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. METHODS: This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. RESULTS: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94). CONCLUSIONS: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

Circulating B vitamins metabolites in depressive disorders - connections with the microbiota-gut-brain axis.

PURPOSE: In this review, we aim to summarize recent information about the association of B vitamins with immune-metabolic aspects of depression and their connection with the gut-brain axis. VIEWS: B vitamins may alter depressive symptoms by many various mechanisms such as reducing oxidative stress, inflammation, gut permeability, controlling epigenetics, modifying the microbiome, and stimulating it to produce many beneficial substances such as short-chain fatty acids or neurotransmitters: norepinephrine, dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine. CONCLUSIONS: Specifically, vitamins B1 (thiamine), B6 (pyridoxine), B9 (folate), and B12 (cyanocobalamin), B2 (riboflavin) have been observed to affect depression. Given probiotic's capability to produce vitamins from the B group, and modify intestinal function, inflammation, or metabolic dysfunction, their supplementation might be a possible treatment method for the immunometabolic form of depression. Thus, the intake of certain probiotic bacterial strains simultaneously with controlling the required daily intake of B vitamins may positively affect the course of depression. Circulating B vitamins metabolite levels, especially B9, B12, and B6 may also be biomarkers of depression. Further investigation is needed to find stronger evidence on this topic.

Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.

Introduction: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy. Methods: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification. Results: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged. Discussion: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

Research progress on Helicobacter pylori infection related neurological diseases.

Helicobacter pylori, a type of gram-negative bacterium, infects roughly half of the global population. It is strongly associated with gastrointestinal disorders like gastric cancer, peptic ulcers, and chronic gastritis. Moreover, numerous studies have linked this bacterium to various extra-gastric conditions, including hematologic, cardiovascular, and neurological issues. Specifically, research has shown that Helicobacter pylori interacts with the brain through the microbiota-gut-brain axis, thereby increasing the risk of neurological disorders. The inflammatory mediators released by Helicobacter pylori-induced chronic gastritis may disrupt the function of the blood-brain barrier by interfering with the transmission or direct action of neurotransmitters. This article examines the correlation between Helicobacter pylori and a range of conditions, such as hyperhomocysteinemia, schizophrenia, Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, migraine, and Guillain-Barré syndrome.

The Gut Microbiota-Brain Axis: A New Frontier in Alzheimer's Disease Pathology.

Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the "two-way" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed.

Gut-directed therapy in Parkinson's disease.

Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.

An integrative exploration of environmental stressors on the microbiome-gut-brain axis and immune mechanisms promoting neurological disorders.

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being.

Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.

Huntington's disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since the HTT protein is involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to the disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations; however, at higher concentrations, they can exacerbate HD by disrupting glial-neuronal communication and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese, and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for the development of a new generation of disease-modifying therapies in HD.

The gut-brain axis in individuals with alcohol use disorder: An exploratory study of associations among clinical symptoms, brain morphometry, and the gut microbiome.

BACKGROUND: Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD. METHODS: We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. RESULTS: Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. CONCLUSIONS: We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

New insights into the effects of serotonin on Parkinson's disease and depression through its role in the gastrointestinal tract.

Neuropsychiatric and neurodegenerative disorders are frequently associated with gastrointestinal (GI) co-pathologies. Although the central and enteric nervous systems (CNS and ENS, respectively) have been studied separately, there is increasing interest in factors that may contribute to conditions affecting both systems. There is compelling evidence that serotonin (5-HT) may play an important role in several gut-brain disorders. It is well known that 5-HT is essential for the development and functioning of the CNS. However, most of the body's 5-HT is produced in the GI tract. A deeper understanding of the specific effects of enteric 5-HT on gut-brain disorders may provide the basis for the development of new therapeutic targets. This review summarizes current data focusing on the important role of 5-HT in ENS development and motility, with particular emphasis on novel aspects of 5-HT signaling in conditions where CNS and ENS comorbidities are common, such as Parkinson's disease and depressive disorders.

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach.

Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, ß-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.

Mild cognitive impairment and microbiota: what is known and future perspectives.

Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.

Dietary Clostridium butyricum and 25-Hydroxyvitamin D3 modulate bone metabolism of broilers through the gut-brain axis.

Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum (C. butyricum) and 25-hydroxyvitamin D3 (25-OH-D3) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators' level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 109 CFU/kg (Cb), basal diet + C. butyricum at 109 CFU/kg and 25-OH-D3 at 25 µg/kg (CbD), or basal diet + 25-OH-D3 at 25 µg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut-brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers.

Shared Genetic Architecture Among Gastrointestinal Diseases, Schizophrenia, and Brain Subcortical Volumes.

BACKGROUND AND HYPOTHESIS: The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. STUDY DESIGN: Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. STUDY RESULTS: The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. CONCLUSIONS: These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases.