The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

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

Emerging evidence suggests a significant role of gut microbiota on neurodevelopmental disorders, including Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD).

Our study aimed to compare gut microbiota composition between these disorders and evaluate the effect of probiotic supplementation.

We conducted a 12-week randomized, double-blind, placebo-controlled trial with 80 children aged 5-14 years (39 with ADHD, 41 with ASD). Baseline and post-intervention fecal samples were analyzed using 16S rRNA gene sequencing to identify changes in gut microbiota composition.

We identified 22 taxa differentiating ADHD and ASD (AUC = 0.939), characterised by increased presence of Clostridia, Ruminococcaceae, and Lachnospiraceae in ADHD, and Bacteroides, Bacilli and Actinobacteria in ASD. These differences remained after accounting for potential confounders. ASD children receiving probiotics had significant increases in Chao 1, Fisher's alpha, and Shannon indices whereas no significant differences in α and β-diversity were found in ADHD. In ADHD, bacteria with potential adverse effects were under-represented. In ASD, the abundance of Eggerthellaceae, and other taxa associated with gastrointestinal problems and anxiety was decreased.

Variations in gut microbiota may influence responses in ADHD and ASD. Probiotic supplementation favorably altered gut microbiota composition, offering insights for future therapeutic strategies targeting the microbiome in neurodevelopmental disorders.

Recent research underscores the role of gut microbiota in ADHD and ASD, indicating that diet can significantly influence microbiota composition and potentially manage these neurodevelopmental disorders. This study reveals distinct differences in gut microbiota composition between children with ADHD and ASD and demonstrates that probiotic supplementation can modulate specific microbial genera in each disorder. These findings pave the way for the development of innovative microbiome-targeted therapies, offering a new avenue for the treatment of neurodevelopmental disorders. Understanding this relationship is crucial for designing future interventions.

There is mounting evidence for the involvement of the immune system, neuroinflammation and disturbed gut microbiota, or dysbiosis, in attention-deficit/hyperactivity disorder (ADHD). Gut dysbiosis is strongly implicated in many physical, autoimmune, neurological, and neuropsychiatric conditions, however knowledge of its particular pathogenic role in ADHD is sparse. As such, this narrative review examines and synthesizes the available evidence related to inflammation, dysbiosis, and neural processes in ADHD. Minimal differences in microbiota diversity measures between cases and controls were found, however many relative abundance differences were observed at all classification levels (phylum to strain). Compositional differences of taxa important to key gut-brain axis pathways, in particular Bacteroides species and Faecalibacterium, may contribute to inflammation, brain functioning differences, and symptoms, in ADHD. We have identified one possible model of ADHD etiopathogenesis involving systemic inflammation, an impaired blood-brain barrier, and neural disturbances as downstream consequences of gut dysbiosis. Nevertheless, studies conducted to date have varied degrees of methodological rigour and involve diverse participant characteristics and analytical techniques, highlighting a need for additional research.

Background/Objectives: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction, communication, and repetitive behaviors. Recent evidence indicates a significant relationship between ASD and imbalances in microbiota, particularly in the oral and gastrointestinal areas. This review examines the impact of oral microbiota, self-injurious behaviors (SIB), sensory sensitivity, and dietary choices on the comorbidities associated with ASD. Methods: An extensive literature review was conducted using PubMed and Scopus. The focus was on human studies with full-text availability, utilizing search terms related to ASD, oral health, oral microbiota, and neurodevelopmental disorders. The research was evaluated for methodological quality and its relevance to the connections between microbiota, oral health, and ASD. Results: Individuals with ASD face unique oral health challenges, including injuries from self-injurious behaviors and increased sensory sensitivity, which complicate oral hygiene and care. Selective eating can lead to nutritional deficiencies and worsen oral health issues. Dysbiosis in oral and gut microbiota, marked by altered levels of acetate, propionate, and butyrate, interferes with gut-brain and oral-brain connections, contributing to behavioral and neurological symptoms. Treatment options such as probiotics, fecal microbiota transfer, and sensory integration therapies can potentially alleviate symptoms and improve quality of life. Conclusions: The relationship between ASD, oral health, and microbiota suggests a bidirectional influence through neuroinflammatory mechanisms and metabolic disturbances. Proactive strategies focusing on microbiota and dental health may help reduce comorbidities and enhance the overall management of ASD, underscoring the need for further research into microbiota-host interactions and their therapeutic potential.

Autism spectrum disorder (ASD) has been associated with disruptions in tryptophan (TRP) metabolism, affecting the production of key neuroactive metabolites. Investigating these metabolic pathways could yield valuable biomarkers for ASD severity and progression. We included 44 children with ASD and 44 healthy children, members of the same family. The average age in the ASD group was 10.7 years, while the average age in the control group was 9.4 years. Urinary tryptophan metabolites were quantified via liquid chromatography-mass spectrometry operating multiple reaction monitoring (MRM). Urinary creatinine was analyzed on an Advia 2400 analyzer using the Jaffe reaction. Statistical comparisons were made between ASD subgroups based on CARS scores. Our findings indicate that children with ASD have higher TRP concentrations (19.94 vs. 16.91; p = 0.04) than their siblings. Kynurenine (KYN) was found at higher levels in children with ASD compared to children in the control group (82.34 vs. 71.20; p = 0.86), although this difference was not statistically significant. The ASD group showed trends of higher KYN/TRP ratios and altered TRP/ indole-3-acetic acid (IAA) and TRP/5-hydroxyindoleacetic acid (5-HIAA) ratios, correlating with symptom severity. Although the numbers of the two groups were different, our findings suggest that mild and severe illnesses involve separate mechanisms. However, further comprehensive studies are needed to validate these ratios as diagnostic tools for ASD.

Modifying gut bacteria in children with autism may influence behaviour, with potential to improve family functioning. We conducted a randomised controlled trial to assess the effect of prebiotics on behaviour, gastrointestinal symptoms and downstream effects on parental quality of life.

Children with autism (4-10yrs) were randomised to 2.4 g/d of prebiotic (GOS) or placebo for six weeks. Pre and post stools samples were collected, and validated questionnaires used to measure change in social and mealtime behaviours, GI symptoms and pQOL. Linear mixed models evaluated group differences for behavioural variables, and Mann Whitney U tests were used to compare change between-groups for GI symptoms, differential abundance of genera and alpha diversity of the microbiome.

Thirty-three parent-child dyads completed the trial. No group difference was seen for behavioural variables but both groups improved significantly from baseline. There was a medium effect size between groups for GI symptoms (d = 0.47) and pQOL (d = 0.44) driven by greater improvements in the prebiotic group. Bifidobacterium increased threefold following prebiotics (1.4-5.9%, p < 0.001) with no change in controls. Supplements were well tolerated, compliance with dose 94%.

Prebiotics modify levels of Bifidobacterium and prove well tolerated but in this instance, resulted in only marginal effects on GI symptoms and pQOL. A larger sample of children with more severe symptoms could help to determine the potential of prebiotics in autism.

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619000615189 .

Dysbiosis of the gut microbiota has been demonstrated in neurodevelopmental disorders but the underlying mechanisms that may explain these associations are poorly understood. Gut secretory immunoglobulin A (SIgA) binds pathogenic microbes, preventing mucosal penetration. Gut microbes also influence SIgA production and its binding characteristics through short-chain fatty acid (SCFA) metabolites, allowing them to regulate the immune response. Serum IgA deficiency has been noted in children with autism spectrum disorders (ASD). In this study, we aimed to determine whether SIgA level in infancy is associated with gut microbiota taxonomy and metabolites, and neurodevelopmental outcomes in preschool children.

For a subsample of 178 children from the Canadian CHILD Cohort Study, gut microbiota of fecal samples collected at 3-4 months and 12 months was profiled using 16S rRNA sequencing. Gut bacterial metabolites levels and SIgA level were measured by nuclear magnetic resonance (NMR) based metabolomics and SIgA enzyme-linked immunosorbent assay at 3-4 months, respectively. Bayley-III Scale of Infant Development was assessed at 12 and 24 months. We evaluated direct relationships in multiple linear regression models and putative causal relationships in statistical mediation models.

Propionate and butyrate levels at 3-4 months were associated with decreased Bayley cognitive score at 24 months (p-values: 0.01 and 0.02, respectively) in adjusted multiple linear regression models, but when we investigated an indirect relationship mediated by decreased SIgA level at 3-4 months, it did not reach statistical significance (p-values: 0.18 and 0.20, respectively). Lactate level at 3-4 months was associated with increased Bayley cognitive score at 24 months in adjusted multiple linear regression models (p-value: 0.01), but the statistical model mediated by increased SIgA level at 3-4 months did not reach statistical significance neither (p-value: 0.20).

Our study contributes to growing evidence that neurodevelopment is influenced by the infant gut microbiota and that it might involve SIgA level, but larger studies are required.

Gut dysbiosis modulates CNS complications and cognitive decline through the gut-brain axis. The study aims to investigate the molecular mechanisms involved in gut dysbiosis-associated cognitive changes and the potential effects of probiotics in high fat-high carbohydrate diet-induced gut dysbiosis-associated neurodegeneration.

We used high fat, high-carbohydrate diet (HFHCD) and high-fat diet (HFD) to induce gut dysbiosis-associated neurodegeneration in C57BL/6 mice. IVIS imaging system and biochemical changes using ELISA measured intestinal inflammation. We used fecal samples for qPCR profiling of intestinal bacteria, and serum was used for inflammatory marker analysis using ELISA. Behavioral studies measured cognitive changes, while histopathology, immunohistochemistry, and western blot analysis of hippocampal samples measured protein changes.

The behavioral studies showed a significant decrease in cognitive function associated with gut dysbiosis in HFHCD and HFD animals. Gut dysbiosis was associated with intestinal inflammation and increased intestinal permeability, followed by systemic and neuroinflammatory changes. Molecular signaling studies showed the involvement of AIM2 inflammasome and cGAS-STING signaling pathways in neurodegeneration for HFHCD animals. Administration of probiotics restored the above processes and prevented gut dysbiosis-associated memory decline in mice.

The study shows that alteration in microbial composition due to prolonged HFHCD could contribute to intestinal inflammation and increased intestinal permeability, facilitating the translocation of microbial toxins like LPS, leading to systemic inflammation, which eventually leads to neuroinflammation and neurodegeneration.

Inflammation has been recognized as a significant factor in the pathophysiology of autism spectrum disorders (ASD), which have garnered increasing scholarly attention over the past few decades. This study aims to explore research trends related to inflammation and ASD through bibliometric analysis.

A comprehensive literature search was conducted in the Web of Science Core Collection (WoSCC) on August 28, 2024. This study was restricted to literature published in English. The bibliometric analysis utilized VOSviewer, CiteSpace, and the R package "bibliometrix" to visualize collaborations, keyword co-occurrences, and emerging research trends.

A total of 1,752 articles addressing inflammation and ASD were published, demonstrating a consistent upward trend in research output. The United States emerged as the country with the highest volume of publications. Saleh A. Bakheet was identified as the most prolific authors, significantly contributing to the literature with 54 publications. The University of California System was recognized as the most productive institution in this area of study. The journal of Brain Behavior and Immunity was noted as a prominent venue for publication in this field, exhibiting high citation metrics that reflect its considerable influence. The keyword "children" was the most frequently occurring term, with other significant terms including "oxidative stress" and "brain." The keyword burst analysis revealed notable periods of increased research focus on topics such as "inflammatory bowel disease," "cytokine production," "neurodevelopmental disorders," and "microbiota."

This bibliometric analysis highlights the growing scholarly attention devoted to the relationship between inflammation and ASD. Significant contributions and emerging trends emphasize the pivotal role of neuroinflammation in ASD, indicating a necessity for further exploration in this domain.

It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses.

To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies.

The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases.

Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials.

The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies.

Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.

The aim of this study is to investigate the impact of using probiotics with strains related to dopamine and gamma-aminobutyric acid production on clinical features of autism spectrum disorder (ASD) and/or attention deficit/hyperactivity disorder (ADHD). This randomized, controlled trial involved 38 children with ADHD and 42 children with ASD, aged 5-16 years, who received probiotics (Lactiplantibacillus plantarum and Levilactobacillus brevis 109/cfu/daily) or placebo for 12 weeks. Parent-reported symptoms were assessed using Conners' 3rd-Ed and the Social Responsiveness Scale Test, 2nd-Ed (SRS-2), and children completed the Conners Continuous Performance Test, 3rd-Ed (CPT 3) or Conners Kiddie CPT, 2nd-Ed (K-CPT 2). Executive functions, quality of life and sleep patterns were also parent-assessed. Intention-to-treat analyses, controlling for sociodemographic and nutritional covariates, revealed no significant inter-group differences in parent-reported or neuropsychological data after the probiotic intervention. However, age-stratified analyses showed improved hyperactivity-impulsivity symptoms in younger children with ASD (Cohen's d = 1.245) and ADHD (Cohen's d = 0.692). Intra-group analyses supported these findings in the aforementioned age and intervention group for both diagnoses. An improvement in impulsivity for children with ASD was also observed in the intra-group analysis of the CPT commissions scores (probiotic: p = 0.001, Cohen's d = -1.216; placebo: p = 0.013, Cohen's d = -0.721). A better comfort score (quality of life) was shown in children with ASD (probiotic: p = 0.010, Cohen's d = 0.722; placebo: p = 0.099, Cohen's d = 0.456). The probiotics used, may improve hyperactivity-impulsivity in children with ASD or/and ADHD and quality of life in children with ASD. Further research is warranted to explore probiotics as an adjunctive therapeutic intervention for NDs.Trial registration: clinicaltrials.gov Identifier: NCT05167110.

Drug-induced dysbiosis, particularly from antibiotics, has emerged as a significant contributor to chronic diseases by disrupting gut microbiota composition and function. Plant-derived secondary metabolites, such as polysaccharides, polyphenols, alkaloids, and saponins, show potential in mitigating antibiotic-induced dysbiosis. This review aims to consolidate evidence from preclinical studies on the therapeutic effects of secondary metabolites in restoring gut microbial balance, emphasizing their mechanisms and efficacy.

A narrative review was conducted using PubMed, Scopus, and Web of Science. Studies were selected based on specific inclusion criteria, focusing on animal models treated with secondary metabolites for antibiotic-induced dysbiosis. The search terms included "gut microbiota", "antibiotics", and "secondary metabolites". Data extraction focused on microbial alterations, metabolite-specific effects, and mechanisms of action. Relevant findings were systematically analyzed and summarized.

Secondary metabolites demonstrated diverse effects in mitigating the impact of dysbiosis by modulating gut microbial composition, reducing inflammation, and supporting host biological markers. Polysaccharides and polyphenols restored the Firmicutes/Bacteroidetes ratio, increased beneficial taxa such as Lactobacillus and Bifidobacterium, and suppressed pathogenic bacteria like Escherichia-Shigella. Metabolites such as triterpenoid saponins enhanced gut barrier integrity by upregulating tight junction proteins, while alkaloids reduced inflammation by modulating proinflammatory cytokines (e.g., TNF-α, IL-1β). These metabolites also improved short-chain fatty acid production, which is crucial for gut and systemic health. While antibiotic-induced dysbiosis was the primary focus, other drug classes (e.g., PPIs, metformin) require further investigation.

Plant-derived secondary metabolites show promise in managing antibiotic-induced dysbiosis by restoring microbial balance, reducing inflammation, and improving gut barrier function. Future research should explore their applicability to other types of drug-induced dysbiosis and validate findings in human studies to enhance clinical relevance.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by challenges in social communication, restricted interests, and repetitive behaviors. It is also associated with a high prevalence of eating disorders, gastrointestinal (GI) symptoms, and alterations in gut microbiota composition. One of the most pressing concerns is food selectivity. Various eating disorders, such as food neophobia, avoidant/restrictive food intake disorder (ARFID), specific dietary patterns, and poor-quality diets, are commonly observed in this population, often leading to nutrient deficiencies. Additionally, gastrointestinal problems in children with ASD are linked to imbalances in gut microbiota and immune system dysregulation. The aim of this narrative review is to identify previous associations between the gut-brain axis and gastrointestinal problems in ASD. We discuss the impact of the "microbiome-gut-brain axis", a bidirectional connection between gut microbiota and brain function, on the development and symptoms of ASD. In gastrointestinal problems associated with ASD, a 'vicious cycle' may play a significant role: ASD symptoms contribute to the prevalence of ARFID, which in turn leads to microbiota degradation, ultimately worsening ASD symptoms. Current data suggest a link between gastrointestinal problems in ASD and the microbiota, but the amount of evidence is limited. Further research is needed, targeting the correlation of a patient's microbiota status, dietary habits, and disease course.

Inflammatory bowel disease (IBD) represents a cluster of chronic idiopathic inflammatory disorders situated at the nexus of intricate interplays. The primary aim of the present investigation is to perform an umbrella review of metaanalyses, systematically offering a comprehensive overview of the evidence concerning risk factors for IBD.

To achieve this, we searched reputable databases, including PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews, from inception through April 2023. Two authors independently assessed the methodological quality of each metaanalysis using the AMSTAR tool and adhered to evidence classification criteria.

In total, we extracted 191 unique risk factors in meta-analyses, including 92 significantly associated risk factors. The top ten risk factors were human cytomegalovirus (HCMV) infection, IBD family history, periodontal disease, poliomyelitis, campylobacter species infection, hidradenitis suppurativa, psoriasis, use of proton pump inhibitors, chronic obstructive pulmonary disease, and western dietary pattern.

In conclusion, this umbrella review extracted 62 risk factors and 30 protective factors, most of which were related to underlying diseases, personal lifestyle and environmental factors. The findings in this paper help to develop better prevention and treatment measures to reduce the incidence of IBD, delay its progression, and reduce the burden of IBD-related disease worldwide.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023417175.

Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize "drug-based" information, which will be ultimately merged to provide clinicians with a "symptom-based" consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. Increasing evidence suggests that it is potentially related to gut microbiota, but no prior bibliometric analysis has been performed to explore the most influential works in the relationships between ASD and gut microbiota. In this study, we conducted an in-depth analysis of the most-cited articles in this field, aiming to provide insights to the existing body of research and guide future directions.

A search strategy was constructed and conducted in the Web of Science database to identify the 100 most-cited papers in ASD and gut microbiota. The Biblioshiny package in R was used to analyze and visualize the relevant information, including citation counts, country distributions, authors, journals, and thematic analysis. Correlation and comparison analyses were performed using SPSS software.

The top 100 influential manuscripts were published between 2000 and 2021, with a total citation of 40,662. The average number of citations annually increased over the years and was significantly correlated to the year of publication (r = 0.481, p < 0.01, Spearman's rho test). The United States was involved in the highest number of publications (n = 42). The number of publications in the journal was not significantly related to the journal's latest impact factor (r = 0.016, p > 0.05, Spearman's rho test). Co-occurrence network and thematic analysis identified several important areas, such as microbial metabolites of short-chain fatty acids and overlaps with irritable bowel syndrome.

This bibliometric analysis provides the key information of the most influential studies in the area of ASD and gut microbiota, and suggests the hot topics and future directions. The findings of this study can serve as a valuable reference for researchers and policymakers, guiding the development and implementation of the scientific research strategies in this area.

The human gut mycobiome, a minor but integral component of the gut microbiome, has emerged as a significant player in host homeostasis and disease development. While bacteria have traditionally been the focus of gut microbiome studies, recent evidence suggests that fungal communities (mycobiota) may also play a crucial role in modulating health, particularly in neuropsychiatric disorders.

This review aims to provide a comprehensive overview of current knowledge on the relationship between the gut mycobiome and neuropsychiatric disorders, exploring the potential of targeting fungal communities as a novel therapeutic strategy.

We summarized recent findings from metagenomic analyses that characterize the diversity and composition of gut mycobiota and discuss how these communities interact with the host and other microorganisms via the gut-brain axis. Key methodologies for studying mycobiota, such as high-throughout sequencing and bioinformatics approaches, were also reviewed to highlight advances in the field.

Emerging research links gut mycobiota dysbiosis to conditions such as schizophrenia, Alzheimer's disease, autism spectrum disorders, bipolar disorder, and depression. Studies indicate that specific fungal populations, such as Candida and Saccharomyces, may influence neuroinflammation, gut permeability and immune responses, thereby affecting mental health outcomes.

Understanding the gut mycobiome's role in neuropsychiatric disorders opens new avenues for therapeutic interventions, including antifungal treatments, probiotics, and dietary modifications. Future research should integrate multi-omics approaches to unravel the complex interkingdom interactions within the gut ecosystem, paving the way for personalized medicine in mental health care.

Autism spectrum disorder (ASD) is a highly heterogeneous disorder characterized by impairments in social, communicative, and restrictive behaviors. Over the past 20 years, research has highlighted the role of the immune system in regulating neurodevelopment and behavior. In ASD, immune abnormalities are frequently observed, such as elevations in pro-inflammatory cytokines, alterations in immune cell frequencies, and dysregulated mechanisms of immune suppression. The adaptive immune system - the branch of the immune system conferring cellular immunity - may be involved in the etiology of ASD. Specifically, dysregulated T cell activity, characterized by altered cellular function and increased cytokine release, presence of inflammatory phenotypes and altered cellular signaling, has been consistently observed in several studies across multiple laboratories and geographic regions. Similarly, mechanisms regulating their activation are also disrupted. T cells at homeostasis coordinate the healthy development of the central nervous system (CNS) during early prenatal and postnatal development, and aid in CNS maintenance into adulthood. Thus, T cell dysregulation may play a role in neurodevelopment and the behavioral and cognitive manifestations observed in ASD. Outside of the CNS, aberrant T cell activity may also be responsible for the increased frequency of immune based conditions in the ASD population, such as allergies, gut inflammation and autoimmunity. In this review, we will discuss the current understanding of T cell biology in ASD and speculate on mechanisms behind their dysregulation. This review also evaluates how aberrant T cell biology affects gastrointestinal issues and behavior in the context of ASD.

The effect of functional variants in long non-coding RNA (lncRNA) gene regions on autism spectrum disorder (ASD) remains unclear. The present study aimed to investigate the association of functional variants located in lncRNA genes with the risk of ASD and explore whether gut microbiota would mediate the relationship. A total of 87 cases and 71 healthy controls were enrolled in the study. MassARRAY platform and 16S rRNA sequencing were respectively applied to assess the genotype of candidate SNPs and gut microbiota of children. The logistic regression models showed that the association between rs2295412 and the risk of ASD was statistically significant after Bonferroni adjustments. The risk of ASD decreased by 19% for each additional C allele carried by children in multiplicative models (OR = 0.81, 95% CI, 0.69-0.94, P = 0.007). Although we identified significant correlations between rs8113922 polymorphisms, Bifidobacteriales, and ASD, the mediating effect of gut microbiota on the relationship of the polymorphisms with the risk of ASD was not significant. The findings demonstrated that functional variants in lncRNA genes play an important role in ASD and gut microbiota could not mediate the association. Future studies are warranted to verify the results and search for more possible mechanisms of variants located in lncRNA genes implicated in ASD.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.

Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders.

In utero exposure to environmental polycyclic aromatic hydrocarbon (PAH) is associated with neurodevelopmental impairments[1-8], prematurity[9-12] and low birthweight[9,13-15]. The gut microbiome serves as an intermediary between self and external environment; therefore, exploring the impact of PAH on microbiota may elucidate their role in disease. Here, we evaluated the effect of in utero PAH exposure on meconium microbiome.

We evaluated 49 mother-child dyads within Fair Start Birth Cohort with full term delivery and adequate meconium sampling. Prenatal PAH was measured using personal active samplers worn for 48 h during third trimester. Post-processing, 35 samples with adequate biomass were evaluated for association between tertile of PAH exposure (high (H) vs low/medium (L/M)) and microbiome diversity.

No significant differences were observed in alpha diversity metrics, Chao1 and Shannon index, between exposure groups for total PAH. However, alpha diversity metrics were negatively associated with log benzo[a]anthracene (BaA) and log chrysene (Chry) with high exposure, but positively associated with log benzo[a]pyrene (BaP) with low/medium exposure. After adjustment for birthweight and sex, alpha diversity metrics were negatively associated with log BaA, BaP, Chry, Indeno (Zhang et al., 2021; Perera et al., 2018)pyrene (IcdP) and total PAH with high exposure. Conversely, with low/medium exposure, alpha diversity metrics positively correlated with log BaP and benzo[b]fluoranthane (BbF). No significant difference in beta diversity was observed across groups using UniFrac, weighted UniFrac, or Bray-Curtis methods. Differential expression analysis showed differentially abundant taxa between exposure groups.

Bacterial taxa were detectable in 35/49 (71%) meconium samples. Altered alpha diversity metrics and differentially abundant taxa between groups suggest in utero PAH exposure may impede early colonization. Sample size is limited, but these findings provide supporting evidence for wider scale research. Research on long-term impact of prenatal PAH exposure on childhood health outcomes is ongoing. Differential effects of specific PAHs need further evaluation.

Autism spectrum disorder is a distinctive developmental condition which is caused by an interaction between genetic vulnerability and environmental factors. Biomarkers play a crucial role in understanding disease characteristics for diagnosis, prognosis, and treatment. This study employs bibliometric analysis to identify and review the 100 top-cited articles' characteristics, current research hotspots and future directions of autism biomarkers.

A comprehensive search of autism biomarkers studies was retrieved from the Web of Science Core Collection database with a combined keyword search strategy. A comprehensive analysis of the top 100 articles was conducted with CiteSpace, VOSviewer, and Excel, including citations, countries, authors, and keywords.

The top 100 cited studies were published between 1988 and 2021, with the United States led in productivity. Core biomarkers such as genetics, children, oxidative stress, and mitochondrial dysfunction are well-established. Potential trends for future research may include brain studies, metabolomics, and associations with other psychiatric disorders.

This pioneering bibliometric analysis provides a comprehensive compilation of the 100 most-cited studies on autism, which not only offers a valuable resource for doctors, and researchers but shedding insights into current shortcomings and future endeavors. Future research should prioritize the application of emerging technologies for biomarkers, longitudinal study of biomarkers, and specificity of autism biomarkers to advance the precision of ASD diagnosis and treatment.

In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.

Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.

Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.

The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiologies, including genetic, environmental, and microbiological factors. In recent years, increasing attention has been given to the role of the gut microbiota in ASD. Emerging evidence suggests that gut microbiota dysbiosis may influence the central nervous system through the gut-brain axis, potentially impacting behavior and neurodevelopment. The use of 16S rRNA gene sequencing has become a pivotal tool in profiling the microbial communities associated with ASD, offering valuable insights into bacterial diversity, composition, and potential functional roles. This review aims to provide a comprehensive analysis of current findings on the relationship between the gut and oral microbiota with ASD, and a particular focus on studies utilizing 16S rRNA sequencing. We will explore how gut microbiome alterations may contribute to ASD pathophysiology, discuss the limitations of existing research, and propose future directions for the integration of microbiome analysis in ASD diagnostics and treatment strategies. These findings underscore the potential role of microbiota in modulating ASD symptoms. The data suggest that specific bacterial taxa are consistently altered in ASD, which may have implications for understanding the gut-brain axis and its influence on neurodevelopment.

Autism spectrum disorder (commonly known as autism) is a complex and prevalent neurodevelopmental condition characterized by challenges in social behavior, restricted interests, and repetitive behaviors. It is projected that the annual cost of autism spectrum disorder in the US will reach USD 461 billion by 2025. However, despite being a major public health problem, effective treatment for the underlying symptoms remains elusive. As numerous literature data indicate the role of gut microbiota in autism prognosis, particularly in terms of alleviating gastrointestinal (GI) symptoms, high hopes have been placed on probiotics for autism treatment. Approximately twenty clinical studies have been conducted using single or mixed probiotic cultures. However, unequivocal results on the effect of probiotics on people with autism have not been obtained. The small sample sizes, differences in age of participants, choice of probiotics, dose and duration of treatment, outcome measures, and analytical methods used are largely inconsistent, making it challenging to draw distinctive conclusions. Here, we discuss the experimental evidence for specific gut bacteria and their metabolites and how they affect autism in light of the phenotypic and etiological complexity and heterogeneity. We propose a personalized medicine approach for using probiotics to increase the quality of life of individuals with autism by selecting specific probiotics to improve particular features of the condition.

People with autism spectrum disorder (ASD) often struggle with gastrointestinal symptoms, implicating alterations of the gut-microbiota-brain axis, which has also been linked to sensory reactivity, pain, and gastro-intestinal symptoms in ASD. To better understand the prevalence and impact of gastrointestinal symptoms among individuals with ASD, a measure is needed that adhere to the Rome IV criteria of gastrointestinal symptoms and is applicable to individuals with ASD. The Gastrointestinal Symptom Severity Scale (GSSS) is a new assessment tool designed to match this need.

In a diverse sample of 265 individuals with ASD (mean age = 9.44, SD = 4.99), we examined the psychometric properties of the GSSS, the prevalence of gastrointestinal symptoms and associations with ASD traits, sensory sensitivity, repetitive behaviors, and pain.

A unidimensional factor structure of the GSSS was confirmed and the measure showed good internal consistency, adequate test-retest reliability and strong convergent validity. Around a third of the participants evidenced clear difficulties with gastrointestinal symptoms and gastrointestinal symptoms were strongly associated with more pronounced ASD traits, sensory reactivity, and repetitive behaviors.

The GSSS shows promise as a useful measure to analyze the prevalence, severity, and impact of gastro-intestinal symptoms in individuals with ASD.

Research on the microbiota-gut-brain axis in autism has primarily focused on bacteria, with limited attention to fungi. There is a growing interest in understanding the involvement of fungi, particularly Candida, in patients with autism spectrum disorder. The aim of this study was to assess the prevalence, antifungal susceptibility profiles and virulence factors of Candida isolates from the guts of Tunisian children with autism. Twenty-eight children with autism and forty-six controls were enrolled. Candida isolates from the faecal samples were identified using biochemical and molecular methods; antifungal susceptibility testing was determined by the EUCAST broth microdilution method and virulence factors, including biofilm formation, cell surface hydrophobicity and phospholipase and proteinase activities, were assessed in vitro. As a result, Candida was detected in 13 children with autism (46.4%) and 14 control children (30.4%). Candida albicans was found to be the most common species isolate in the faeces of both groups of children. Antifungal susceptibility profiles showed that one Candida isolate was resistant to amphotericin B and anidulafungin (3.7%), six were resistant to micafungin (22.2%) and five were resistant to fluconazole (18.5%). All Candida isolates were biofilm producers. Of the twenty-seven isolates, only four showed phospholipase activity (14.8%), eight showed aspartyl-proteinase activity (29.6%) and nine were hydrophobic (33.3%). These results highlight the presence of Candida in the guts of children with autism, as well as the ability to express multiple virulence factors and the antifungal resistance, and they emphasize the need for further studies to confirm intestinal Candida colonization and its potential role in autism.

Small intestinal bacterial overgrowth (SIBO) is a gastrointestinal condition characterized by abnormal colonization of bacteria in the small intestine, leading to overgrowth and alteration, which is linked to gastrointestinal issues, potentially affecting neurological and mental health. Despite existing research, we still do not understand how SIBO affects tryptophan metabolism and psychiatric diseases. We investigated the literature for connections between SIBO, tryptophan metabolism disruptions, and psychiatric disorders like autism, schizophrenia, Alzheimer's, and Parkinson's diseases. We also explored the interaction between thyroid disorders and their influence on SIBO and psychiatric illnesses. PubMed and Google Scholar databases were searched using keywords and phrases, individual and in combinations, like "SIBO," "gut microbiota," "neurologic disorders," "mental disorders," "tryptophan," "dopamine," and "thyroid disease." We focused on original research and review papers that presented empirical studies conducted on animal models and human subjects published in English between February 1992 to February 2023. The initial 2 634 534 records were preliminary screened based on title and abstract and then subjected to full-text review to exclude publications with insufficient data on SIBO, lack of a psychiatric disorder component, or methodological limitations compromising the integrity of the findings. The analysis highlights the significance of the association between psychiatric disorders and SIBO, emphasizing the role of gut-microbial diversity in mental health. We advocate for more detailed studies, including longitudinal research, to clarify the causal relationships between SIBO, gut dysbiosis, and psychiatric disorders and for an integrated approach while treating complex psychiatric conditions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits. Accumulated evidence has shown a link between alterations in the composition of gut microbiota and both neurobehavioural and gastrointestinal symptoms in children with ASD which are related to the genera Lactobacillus and Bifidobacterium. These genera have been recently categorized as "psychobiotics". Moreover, this study aimed to compare the relative abundance of psychobiotics (L. plantarum, L. reuteri, and B. longum) to the total gut microbiome in typically developing (TD) children and those with ASD in order to correlate the distribution of psychobiotic with the severity and sensory impairments in autism. The ASD children were assessed using the Childhood Autism Rating Scale (CARS), while sensory impairments were evaluated using the Short Sensory Profile (SSP). Furthermore, the gut microbiome was analyzed using the quantitative real-time PCR. The study revealed a statistically significant increase in the relative abundance of L. reuteri and L. plantarum in the TD group in comparison to ASD children. Regarding the SSP total score of ASD children, a statistically significant negative correlation was found between both Lactobacillus and L. plantarum with the under-responsive subscale. For the Autism Treatment Evaluation Checklist (ATEC) score, B. longum and Lactobacillus showed a significant positive correlation with Health/Physical/Behaviour.

Alterations of the microbiome-gut-brain (MGB) axis have been associated with autism spectrum disorder (ASD) and disorders of gut-brain interaction (DGBI). DGBI are highly prevalent in autistic children and are associated with worsening behaviour and anxiety. Treatments such as probiotics, prebiotics and gut-directed hypnotherapy (GDH) have shown efficacy in improving gut symptoms in children. The primary objective of the study was to compare changes in gastrointestinal (GI) scores following a 12-week intervention of synbiotics (prebiotic + probiotic) +/- GDH with a follow-up at 24 weeks. Secondary objectives included changes in behavioural and anxiety symptoms, while changes in gut microbiome composition were assessed as an exploratory objective. Children diagnosed with ASD aged 5.00-10.99 years (n = 40) were recruited and randomised (1:1) to a 12-week intervention of either synbiotics (SYN group) or synbiotics + GDH (COM group). Both the SYN and COM group experienced significant reductions in total GI scores post-intervention and at follow-up (p < 0.001), with no superiority of the COM treatment over the SYN treatment. The COM group showed beneficial reductions in anxiety scores (p = 0.002) and irritability behaviours (p < 0.001) which were not present in the SYN group. At follow-up, only those in the COM group maintained significant reductions in GI pain scores (p < 0.001). There were significant changes in gut microbiota such as increases in Bifidobacterium animalis and Dialister in both groups over time. In conclusion, synbiotics with or without GDH may help support standard care for autistic children who suffer comorbid DGBI. The trial was prospectively registered at clinicialtrials.gov on 16 November 2020 (NCTO4639141).

The infant gut microbiota undergoes significant changes during early life, which are essential for immune system maturation, nutrient absorption, and metabolic programming. Among the various microbial metabolites, short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, produced through the fermentation of dietary fibers by gut bacteria, have emerged as critical modulators of host-microbiota interactions. SCFAs serve as energy sources for colonic cells and play pivotal roles in regulating immune responses, maintaining gut barrier integrity, and influencing systemic metabolic pathways. Recent research highlights the potential neuroprotective effects of SCFAs in pediatric populations. Disruptions in gut microbiota composition and SCFA production are increasingly associated with a range of pediatric health issues, including obesity, allergic disorders, inflammatory bowel disease (IBD), and neurodevelopmental disorders. This review synthesizes current knowledge on the role of microbiota-derived SCFAs in pediatric health, emphasizing their contributions from gut development to neuroprotection. It also underscores the need for further research to unravel the precise mechanisms by which SCFAs influence pediatric health and to develop targeted interventions that leverage SCFAs for therapeutic benefits.

Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction.

We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder.

Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe.

By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.