Gut microbiota in early pediatric multiple sclerosis: a case-control study. - PubMed - NCBI

BACKGROUND AND PURPOSE:
Alterations in the gut microbial community composition may be influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex.

METHODS:
Children ≤18 years old within 2 years of MS onset or controls without autoimmune disorders attending a University of California, San Francisco, USA, pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance, were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression.

RESULTS:
Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range 4-18) were studied. Cases had a short disease duration (mean 11 months; range 2-24) and half were immunomodulatory drug (IMD) naïve. Whilst overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, P < 0.02). However, relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all P and q < 0.000005). Microbial genes predicted as enriched in MS versus controls included those involved in glutathione metabolism (Mann-Whitney, P = 0.017), findings that were consistent regardless of IMD exposure.

CONCLUSIONS:
In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu."




Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor : Nature Medicine

Astrocytes have important roles in the central nervous system (CNS) during health and disease. Through genome-wide analyses we detected a transcriptional response to type I interferons (IFN-Is) in astrocytes during experimental CNS autoimmunity and also in CNS lesions from patients with multiple sclerosis (MS). IFN-I signaling in astrocytes reduces inflammation and experimental autoimmune encephalomyelitis (EAE) disease scores via the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) and the suppressor of cytokine signaling 2 (SOCS2). The anti-inflammatory effects of nasally administered interferon (IFN)-β are partly mediated by AHR. Dietary tryptophan is metabolized by the gut microbiota into AHR agonists that have an effect on astrocytes to limit CNS inflammation. EAE scores were increased following ampicillin treatment during the recovery phase, and CNS inflammation was reduced in antibiotic-treated mice by supplementation with the tryptophan metabolites indole, indoxyl-3-sulfate, indole-3-propionic acid and indole-3-aldehyde, or the bacterial enzyme tryptophanase. In individuals with MS, the circulating levels of AHR agonists were decreased. These findings suggest that IFN-Is produced in the CNS function in combination with metabolites derived from dietary tryptophan by the gut flora to activate AHR signaling in astrocytes and suppress CNS inflammation."



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Too much folate in pregnant women increases risk for autism, study suggests

Women who plan on becoming pregnant are told they need enough of the nutrient folate to ensure proper neurodevelopment of their babies, but new research from the Johns Hopkins Bloomberg School of Public Health suggests there could be serious risks in having far too much of the same nutrient.

The researchers found that if a new mother has a very high level of folate right after giving birth - more than four times what is considered adequate - the risk that her child will develop an autism spectrum disorder doubles. Very high vitamin B12 levels in new moms are also potentially harmful, tripling the risk that her offspring will develop an autism spectrum disorder. If both levels are extremely high, the risk that a child develops the disorder increases 17.6 times. Folate, a B vitamin, is found naturally in fruits and vegetables, while the synthetic version, folic acid, is used to fortify cereals and breads in the United States and in vitamin supplements.



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Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index: JAMA Pediatrics

Importance
The consumption of artificial sweeteners has increased substantially in recent decades, including among pregnant women. Animal studies suggest that exposure to artificial sweeteners in utero may predispose offspring to develop obesity; however, to our knowledge, this has never been studied in humans.
 Objective  To determine whether maternal consumption of artificially sweetened beverages during pregnancy is associated with infant body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]).
Design, Setting, and Participants  This cohort study included 3033 mother-infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based birth cohort that recruited healthy pregnant women from 2009 to 2012. Women completed dietary assessments during pregnancy, and their infants’ BMI was measured at 1 year of age (n = 2686; 89% follow-up). Statistical analysis for this study used data collected after the first year of follow-up, which was completed in October 2013. The data analysis was conducted in August 2015.
Exposures  Maternal consumption of artificially sweetened beverages and sugar-sweetened beverages during pregnancy, determined by a food frequency questionnaire.
Main Outcomes and Measures  Infant BMI z score and risk of overweight at 1 year of age, determined from objective anthropometric measurements and defined according to World Health Organization reference standards.
Results  The mean (SD) age of the 3033 pregnant women was 32.4 (4.7) years, and their mean (SD) BMI was 24.8 (5.4). The mean (SD) infant BMI z score at 1 year of age was 0.19 (1.05), and 5.1% of infants were overweight. More than a quarter of women (29.5%) consumed artificially sweetened beverages during pregnancy, including 5.1% who reported daily consumption. Compared with no consumption, daily consumption of artificially sweetened beverages was associated with a 0.20-unit increase in infant BMI z score (adjusted 95% CI, 0.02-0.38) and a 2-fold higher risk of infant overweight at 1 year of age (adjusted odds ratio, 2.19; 95% CI, 1.23-3.88). These effects were not explained by maternal BMI, diet quality, total energy intake, or other obesity risk factors. There were no comparable associations for sugar-sweetened beverages.
Conclusions and Relevance  To our knowledge, we provide the first human evidence that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI. Given the current epidemic of childhood obesity and widespread use of artificial sweeteners, further research is warranted to confirm our findings and investigate the underlying biological mechanisms, with the ultimate goal of informing evidence-based dietary recommendations for pregnant women."



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Epigenetic study of lactose intolerance may shed light on the origin of mental illness - Medical News Today

Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut–brain mechanisms.



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Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: potential role of enhanced maternal immune activity? - PubMed - NCBI

Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case-control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N=43) and pregnant women with healthy offspring (controls, N=95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p<0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis.



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Ketamine lifts depression via a byproduct of its metabolism | National Institutes of Health (NIH)

"A chemical byproduct, or metabolite, created as the body breaks down ketamine likely holds the secret to its rapid antidepressant action, National Institutes of Health (NIH) scientists and grantees have discovered.  This metabolite singularly reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative, or addictive side effects associated with ketamine. It may work via AMPA receptor stimulation rather than by NMDA receptor antagonism.



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Yeast infection linked to mental illness: Schizophrenia and bipolar disorder

In a study prompted in part by suggestions from people with mental illness, Johns Hopkins researchers found that a history of Candida yeast infections was more common in a group of men with schizophrenia or bipolar disorder than in those without these disorders, and that women with schizophrenia or bipolar disorder who tested positive for Candida performed worse on a standard memory test than women with schizophrenia or bipolar disorder who had no evidence of past infection."




Patients with rosacea have increased risk of dementia.

OBJECTIVE:

Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and peptides
 (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers.

METHODS:

All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs).

RESULTS:

The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period, of whom 29,193 were diagnosed with AD. The adjusted HRs of dementia and AD were 1.07 (95% confidence interval [CI] = 1.01-1.14), and 1.25 (95% CI = 1.14-1.37), respectively, in patients with rosacea. Stratified by sex, the HRs of AD were 1.28 (95% CI = 1.15-1.45) and 1.16 (95% CI = 1.00-1.35) in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals ≥60 years old (adjusted HR = 1.20, 95% CI = 1.08-1.32). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 (95% CI = 1.17-1.72) and 1.92 (95% CI = 1.44-2.58), respectively.

INTERPRETATION:

Rosacea is significantly associated with dementia, particularly AD. Increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant.

Aerial pesticide exposure increases the risk of developmental delay and Autism spectrum disorder

BACKGROUND:

Pesticides are one environmental factor implicated in developmental delay (DD) and autism spectrum disorder (ASD). The influence of the timing and route of pesticide exposure on the risk of ASD/DD is not well defined.

OBJECTIVE: We identified an area of Central New York (NY) with unique pyrethroid pesticide (PP) exposure to study these factors. Each summer, to combat mosquito-borne encephalitis in the Cicero Swamp region, the Department of Health uses airplanes to apply PPs. In contrast, surrounding areas are exposed to standard methods of pesticide application, such as controlled droplet application, by commercial applicators. The objective of this study was to determine if the amount, route or gestational timing of pesticide exposure influenced the risk of ASD/DD.

DESIGN/METHODS: A retrospective review of records from a tertiary referral center was used to estimate the number of children with ASD/DD from 24 zip codes within Central NY from March, 2010 to March, 2015. Cases were identified using ICD-9 codes for ASD or DD at 6 affiliated pediatric clinics. To control for referral bias, rates of 4 common diagnoses were calculated for each zip code. Publicly available mandated reporting data from the Department of Environmental Conservation were used to quantify pesticide exposure (kg) among zip codes. The 2013 American Community Survey was used to quantify demographic data. Data from the 8 zip codes exposed to yearly aerial PPs were compared with 16 control zip codes.

RESULTS: There was no significant difference between aerial-exposed and control groups in number of children, overall births, premature births, poverty level, or child sex. The referral rate from aerial-exposed zip codes was lower for all 4 control diagnoses. The aerial-exposed zip codes had higher levels of total pesticide exposure (p = 0.047), but no difference in pesticide use per square km (p = 0.10). The relative risk of ASD/DD for children in zip codes with aerial spraying was 1.25 (95% CI = 1.025-1.506). ASD/DD prevalence correlated with aerial PP exposure (r = 0.58) and total pesticide exposure (r = 0.41). There was no correlation between gestational age during aerial spraying and ASD/DD prevalence (r = -0.034).

CONCLUSIONS: Exposure to pesticides is correlated with increased risk of ASD/DD. The relative risk of ASD/DD increases when PP exposure occurs through aerial application, but the gestational timing of this exposure does not influence ASD/DD risk."



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Even a little air pollution may have long-term health effects on developing fetus

 Even small amounts of air pollution appear to raise the risk of a condition in pregnant women linked to premature births and lifelong neurological and respiratory disorders in their children, new Johns Hopkins Bloomberg School of Public Health research suggests.
Fine particles from car exhaust, power plants and other industrial sources are breathed into the lungs, but the scientists have now found evidence of the effects of that pollution in the pregnant women's placentas, the organ that connects her to her fetus and provides blood, oxygen and nutrition. They found that the greater the maternal exposure to air pollution, the more likely the pregnant women suffered from a condition called intrauterine inflammation, which can increase the risk of a number of health problems for her child from the fetal stage well into childhood.



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Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment: Immunity

Highlights
•Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier
•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior
•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes
•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy."



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Body’s defenses against common viruses may mess up neurons, spark depression | Ars Technica

Getting sick is definitely a bummer. But besides feeling icky and being stuck in bed, viral infections may cause us to actually be depressed. While scientists have been clued into this connection for a while, there was little data on how everyday viral infections, like the flu, might mess with our moods.

Now, data from a new mouse study shows that common viruses may spur sadness by causing the cells that line the blood-brain barrier to release signals that hush the chatter between neurons in the area of the brain responsible for mood. The findings, published this week in the journal Immunity, may finally explain the link between infections and mental health problems, and it could point researchers towards new strategies for treating depression and other mood disorders.

Researchers have been collecting hints of the connection between mental health and infections for years. Though it was first dismissed as people simply being blue about getting sick, doctors now accept that there is a condition called “sickness behavior.” This condition is marked by cognitive deficits, drowsiness, general malaise, and other depression-like symptoms in those with an infection. Moreover, in a 2013 Danish study, researchers found that people who had been treated for a severe infection were 62 percent more likely to suffer from mood disorders. Perhaps related, those that had an autoimmune disease were 45 percent more likely to have such a mental health issue."



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Fructose alters hundreds of brain genes, which can lead to a wide range of diseases | UCLA

Fructose alters hundreds of brain genes, which can lead to a wide range of diseases | UCLA: "A range of diseases — from diabetes to cardiovascular disease, and from Alzheimer’s disease to attention deficit hyperactivity disorder — are linked to changes to genes in the brain. A new study by UCLA life scientists has found that hundreds of those genes can be damaged by fructose, a sugar that’s common in the Western diet, in a way that could lead to those diseases.

However, the researchers discovered good news as well: An omega-3 fatty acid known as docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose."



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Pancreatic cancer risk linked to changes in mouth bacteria - Medical News Today

The participants were taking part in larger, ongoing studies of cancer risk, where they had been given mouthwash samples when they joined the studies. They were followed for nearly 10 years, during which any cancer diagnoses were noted.

When they analyzed the results, Prof. Ahn and colleagues found that participants whose mouth bacteria contained either of two certain types had a higher risk of developing pancreatic cancer, compared with participants whose oral microbiome showed no evidence of the microorganisms.

Specifically, they found presence of Porphyromonas gingivalis was linked to a 59% overall higher risk of developing pancreatic cancer. Similarly, presence of Aggregatibacter actinomycetemcomitans was linked to a 50% overall higher risk. Both types of bacteria are known to be associated with gum disease or periodontitis."


A Systematic Review and Meta-Analysis of the Association between Helicobacterpylori Infection and Dementia - IOS Press

A positive association between Helicobacter pylori infection and dementia has been reported, yet findings are inconsistent.

Objective:To examine the association between H. pylori infection and dementia. Methods:A literature search was performed using the databases OVID-Medline, Institute of Scientific Information Web of Science, and EMBASE. The meta-analysis was conducted using the random effects model. The primary analysis included studies in which the exposure variable was presence of H. pylori infection (yes versus no) and the outcome was incident dementia (yes versus no), which was pre-selected as the end-result of gradual cognitive decline overtime. Publication bias was explored using funnel plot and the Egger regression intercept.

Results:A total of 260 records were identified; 13 addressed cognition and/or dementia in relation to H. pylori infection, of which only seven were included in the meta-analysis. The primary analysis showed a significant positive association between H. pylori infection and dementia; pooled odds ratio 1.71 (95% CI 1.17–2.49) (pv = 0.01). No significant evidence of publication bias was found. Conclusions:H. pylori may play a role in the etiology of dementia. Identification of the biological mechanisms of such association is needed, as well as assessment of the impact of H. pylori therapy on the risk and progression of dementia."



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Bisphenol A in low doses can affect the reproductive system , obesity, and behaviour

"If rats are exposed to bisphenol A in low doses during early development it can lead to reduced sperm count, obesity and changes to breast development and behaviour. These are some of the findings of a new study from the National Food Institute, Technical University of Denmark. The results support previous animal studies, which have shown that low doses of bisphenol A can affect development of the metabolism as well as the reproductive and nervous systems."



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Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment: Immunity

 Highlights 

•Viruses induce depressive behavior and ISG15 expression at the blood-brain barrier
•IFNAR1 expression on neural cells is not involved in IFN-β-induced sickness behavior
•IFNAR1 expression on brain endothelial and epithelial cells drives behavioral changes
•Brain endothelia- and epithelia-derived CXCL10 inhibits hippocampal synaptic plasticity

Summary 

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy."



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Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host|[rsquo]|s metabolism : Molecular Psychiatry

"Major depressive disorder (MDD) is the result of complex gene–environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with ‘depression microbiota’ derived from MDD patients resulted in depression-like behaviors compared with colonization with ‘healthy microbiota’ derived from healthy control individuals. Mice harboring ‘depression microbiota’ primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host’s metabolism."



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