Biology subjects

Richard, J.-R.

Publications and source records attributed to Richard, J.-R..

3 recordsLinked to original sources

bioRxiv2026

Fecal extracellular vesicles from adults with autism spectrum disorder affect mouse behavior and gut motility by targeting the neuronal nitrergic pathway

Beside behavioral symptoms, many patients with autism spectrum disorder (ASD) present gastrointestinal disorders and gut microbiota dysbiosis. In order to better understand the mechanisms underlying microbiota-gut-brain interactions in ASD, we isolated fecal extracellular vesicles (EVs), as a source of microbiota-derived EVs, from control individuals (f-EV-CTL) and patients with ASD (f-EV-ASD) to study in mice their impact on brain and gut. The f-EV-ASD induced hypersocial and anxiolytic-like behavior, and reduced gastrointestinal transit time compared to mice treated with f-EV-CTL. In the colon, f-EV-ASD altered motility through the enteric neuronal nitric oxide (NO)-sensitive component. f-EV-ASD potentiated NO signaling and disrupted intracellular calcium dynamics in enteric neurons. This effect was mediated by butyrate and valerate through FFAR3 receptor. Our findings establish fecal EVs as critical mediators of microbiota-host communication, linking microbial metabolites to altered behavior and gut function and identifying a potential mechanism underlying ASD pathophysiology.

physiology↗

bioRxiv2026

Microbial metabolite p-cresol associates with constipation in adults with high-functioning autism spectrum disorder and induces constipation-like symptoms in mice

Gastrointestinal (GI) symptoms are prevalent in Autism Spectrum Disorder (ASD), yet their biological correlates remain poorly understood. The gut microbial metabolite p-cresol is reported to be elevated in ASD, but its link to specific GI symptoms in adult high-functioning adults remains unexplored. We examined the relationship between serum levels of p-cresol and its conjugates (p-cresol sulfate, p-cresol glucuronide) with five common GI symptoms (diarrhea, constipation, abnormal stool aspect, bloating, abdominal pain) in 272 adults with high-functioning ASD. Clinical and dietary assessments were performed, and serum metabolites were measured using targeted metabolomics in 177 patients. Females with ASD had higher rates of GI symptoms and elevated p-cresol compared to males. Multivariable regression analysis showed that serum p-cresol, but not its conjugates, was selectively associated with constipation frequency, independent of sex, age, and diet. No associations were observed with the other GI symptoms. In mice, chronic p-cresol exposure induced constipation-like GI dysfunction, supporting a causal link. These findings identify p-cresol as a possible mediator of constipation in ASD. This work supports the development of tailored interventions for GI symptoms in adults with ASD. LAY SUMMARYPeople with autism spectrum disorder (ASD) often experience gastrointestinal (GI) symptoms, but the role of the gut microbiota remains unclear. Elevated levels of p-cresol, a gut microbiota-derived molecule, have been reported in ASD, though its link to specific GI symptoms, particularly in adults, remains unknown. We studied 272 adults with high-functioning ASD and we found that women with ASD reported more frequently GI symptoms and had higher levels of p-cresol than men. Higher p-cresol levels were associated with more frequent constipation, but not with other GI symptoms. In mice, p-cresol treatment induced signs of constipation, suggesting a causal role. Overall, our findings indicate that p-cresol may contribute to constipation in adults with ASD and support the need personalized medical approaches to digestive health in adults with ASD.

microbiology↗

bioRxiv2023

Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder

ImportanceExamining translatable mitochondrial blood-based biological markers to identify its association with metabolic diseases in bipolar disorder. ObjectiveTo test whether mitochondrial metabolites, mainly lactate, and cell-free circulating mitochondrial DNA are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. DesignIn a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder was conducted, including baseline plasma samples and blinded observers for all experimentation and analysis. SettingThe FondaMental Foundation coordinate a multicenter, multidisciplinary French networks aiming at creation of cohorts to improve identification of homogeneous subgroups of psychiatric disorders toward personalized treatments. ParticipantsThe FACE-BD primary testing cohort includes 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 235 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Participants were randomly selected based on biosample availability. ExposuresAll patients underwent the standard primary care within their center. No intentional exposures were part of this study. Main Outcome and MeasuresThe primary outcome modelled an association with lactate and metabolic syndrome in this population. Reflective a priori hypothesis. ResultsMultivariable regression analyses show lactate association with triglycerides (Est= 0.072(0.023), p = 0.0065,), fasting glucose (Est = 12(0.025), p= 0.000015) and systolic (Est= 0.003(0.0013), p= 0.031) and diastolic blood pressure (Est = 0.0095{+/-}0.0017, p= 1.3e-7). Significantly higher levels of lactate were associated with presence of metabolic syndrome (Est = 0.17{+/-}0.049, p=0.00061) after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. Conclusion & RelevanceThis thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, whereas circulating cell-free mitochondrial DNA is limited in the context of metabolic syndrome. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities. Key PointsO_ST_ABSQuestionC_ST_ABSCan lactate, a mitochondrial metabolite, indicate metabolic syndrome in bipolar disorder? FindingIn 837 stable bipolar disorder patients, we found high lactate levels significantly associated with metabolic syndrome, unlike circulating cell-free mitochondrial DNA. This pattern also appeared in acute bipolar and schizophrenia cases. Mitochondrial-targeted metabolomics distinguishes patients with high lactate and metabolic syndrome from those without lactate changes, but presence of metabolic syndrome. MeaningThis research underscores lactate as a potential biomarker for identifying bipolar disorder patients with metabolic syndrome. It opens new avenues for personalized treatment strategies, leveraging mitochondrial metabolite profiling to improve patient stratification and therapeutic outcomes.

neuroscience↗