Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

Improvement in Gastrointestinal and Health-related Quality of Life Outcomes After Conversion From Mycophenolate Mofetil to Enteric-coated Mycophenolate Sodium in Liver Transplant Recipients

Functional gastrointestinal disorders have a multifactorial etiology, including somatic and psychosocial factors. We provide multidisciplinary outpatient consultations by a gastroenterologist and a psychiatrist using an integrated approach toward somatic and psychosocial factors in complex functional gastrointestinal disorders. The aim of this study was to determine the efficacy of this approach assessing gastrointestinal and psychiatric symptoms and quality of life. All patients with complex functional gastrointestinal disorders visiting for consultation were included and treated with antidepressants, psychotherapy, or both, or given advice for treatment in their own region. Questionnaires testing gastrointestinal and psychiatric symptoms, and quality of life at first visit and after 6 and 12 months were completed. A total of 124 patients were included (70% women, mean age 48 years): 57% were diagnosed with irritable bowel syndrome and about 80% had a psychiatric diagnosis (50% anxiety disorder, 20% mood disorder). Of the patients, 57% were treated with antidepressants and psychotherapy, 6% with psychotherapy alone, and 38% received advice for treatment in their own region. After 1 year, patients showed significant improvement in all questionnaires, with the exception of those testing gastrointestinal symptoms, although there were significant improvements in these at 6 months. This is the first prospective study on the efficacy of an integrated medical-psychiatric outpatient care model in patients with complex functional gastrointestinal disorders, showing significant improvement in gastrointestinal and psychiatric symptoms as well as quality of life after 6 months. With the exception of improvement in gastrointestinal symptoms, improvement persisted at the 1-year follow-up. This indicates that longer follow-up focusing on gastrointestinal symptoms may be needed.

Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including Prevotella (P. dentalis, P. enoeca, P. oris, P. meloninogenica), Bifidobacterium bifidum, and a sulfur reducer Desulfovibrio piger increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.

Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the ASD group. MTT drove global shifts in plasma profiles across various metabolic features, including nicotinate/nicotinamide and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct.IMPORTANCE Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers.

Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota–gut–brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability (“leaky gut”) and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut–brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD.

ECT FOR THE TREATMENT OF SOMATIC SYMPTOM DISORDER AND UNINTENTIONAL WEIGHT LOSS IN OLDER ADULTS: 2 CASE REPORTS

Changes in Fecal Calprotectin After Rifaximin Treatment in Patients With Nonconstipated Irritable Bowel Syndrome

Current diagnosis of autism spectrum disorder (ASD) is based on assessment of behavioral symptoms, although there is strong evidence that ASD affects multiple organ systems including the gastrointestinal (GI) tract. This study used Fisher discriminant analysis (FDA) to evaluate plasma metabolites from 18 children with ASD and chronic GI problems (ASD + GI cohort) and 20 typically developing (TD) children without GI problems (TD − GI cohort). Using three plasma metabolites that may represent three general groups of metabolic abnormalities, it was possible to distinguish the ASD + GI cohort from the TD − GI cohort with 94% sensitivity and 100% specificity after leave-one-out cross-validation. After the ASD + GI participants underwent Microbiota Transfer Therapy with significant improvement in GI and ASD-related symptoms, their metabolic profiles shifted significantly to become more similar to the TD − GI group, indicating potential utility of this combination of plasma metabolites as a biomarker for treatment efficacy. Two of the metabolites, sarcosine and inosine 5′-monophosphate, improved greatly after treatment. The third metabolite, tyramine O-sulfate, showed no change in median value, suggesting it and correlated metabolites to be a possible target for future therapies. Since it is unclear whether the observed differences are due to metabolic abnormalities associated with ASD or with GI symptoms (or contributions from both), future studies aiming to classify ASD should feature TD participants with GI symptoms and have larger sample sizes to improve confidence in the results.

Background: Helicobacter pylori (H. pylori) infection has become a remarkable worldwide health problem. The eradication of H. pylori has become a challenge. Probiotics have proven beneficial in reducing the side effects and increases patient compliance. Lactobacillus reuteri (L. reuteri) is frequently used probiotic and considered safe for human consumption. The aim of this study was to compare the effectiveness of a probiotic and conventional antibiotic triple therapy in the management of H. pylori infection.
 Methods: This was a prospective observational study carried out for a period of six months. Patient data were extracted from their medical records. Treatment outcome was evaluated based on the report of Rapid Urease Test (RUT). Symptoms were assessed using Gastrointestinal Symptom Rating Scale (GSRS). Descriptive statistics were used to summarize patient characteristics. T-test, chi square test and one way ANOVA were used wherever appropriate.
 Results: A total of 105 patients with confirmed H. pylori infection were included, of which 42% were males and 58% were females. The mean age of three group patients were 38.03±10.68, 34.00±13.36 and 36.11±13.37 years. Eradication rate noted in Lactobacillus reuteri only treatment was 86%, eradication rate noted in Lactobacillus reuteri+ ppi was 86% and in antibiotic group was 92%. Patients with three different treatments have shown significant improvement in gastrointestinal symptoms (p < 0.001).
 Conclusion: The overall data suggest that L. reuteri is recommended for a better eradication rate and reduced gastrointestinal symptoms. Though conventional triple therapy of H. pylori has shown an increased eradication rate and significant improvement in gastrointestinal symptoms, there was no great difference when compared with L. reuteri treated patients.
 Keywords: H. pylori, Triple therapy, L. reuteri, Eradication, Gastrointestinal symptoms

Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82–88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.

Isolated Gastrointestinal Alpha-gal Meat Allergy Is a Cause for Gastrointestinal Distress Without Anaphylaxis

Background and Aims: There is a high prevalence of gastrointestinal-related (GI) symptoms among children with autism spectrum disorder (ASD), which is associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a proposed therapeutic strategy that aims to address the dysregulation of the gut microbiome among children with ASD. Our study performed the first systematic review aimed to evaluate the benefits of FMT on the behavioral and gastrointestinal symptoms of pediatric patients with autism. Methods: A literature search was performed using variations of the keywords "pediatrics" and "fecal microbiota transplantation" in PubMed, EMBASE, CINAHL, Cochrane, and Web of Science from inception to 30 June 2022. Four studies that met the eligibility criteria were included in the systematic review. The efficacy of FMT on behavioral symptoms was measured by the difference in Aberrant Behavior Checklist (ABC) and Child Autism Rating Scale (CARS) scores before and after FMT. Results: We found a statistically significant improvement (p < 0.05) in ABC and CARS scores following FMT, with a statistically significant decrease in scores observed across all studies. In addition, substantial improvements in gastrointestinal symptoms were observed across all studies. Conclusion: Our findings suggest that FMT may offer a promising intervention for treating both behavioral and gastrointestinal symptoms in pediatric patients with autism.

Background: Different treatments have been developed and used to control symptoms and improve quality of life in patients with digestive diseases and disorders. Although the use of drugs or alternative approaches has improved symptom severity in some but not all patients, often these improvements were not sustainable. Objectives: An open label clinical study was initiated to determine if oral capsules containing a dietary supplement of herbs and oils (GI RegenerateTM) could reduce self-reported gastrointestinal symptoms and improve quality of life (QOL) indicators in patients with gastrointestinal conditions. Methods: Participants included 50 patients (40 females and 10 males) of mean age of 51.1 ± 12.7 years (range, 24 - 77 years) with a diagnosis of a gastrointestinal disorder or gastrointestinal symptoms. These patients consumed five soft-gels containing the test supplement 30 minutes before each meal for 90 days. Symptoms were evaluated by medical staff, and patient health status was self-reported using a validated quality of life questionnaire (Quality of Life Digestive Survey) designed for functional digestive disorders. Exit interviews (Patient Global Impression of Change, PGIC) were conducted by the medical staff. Results: Participants in the study responded with improved symptom severities and QOL scores to the test dietary supplement within the 90 day period; most improvements occurred within 20 days on the test dietary supplement. By the end of the study there were significant overall global improvements in the symptoms and QOL health surveys (p = 0.0183), with significant improvements in symptom discomfort (p = 0.0004), daily activities (p = 0.029) and anxiety (p = 0.018). In contrast, there were insignificant improvements in diet (p = 0.398), sleep (p = 0.136), health perception (p = 0.686), coping with the disease (p = 0.309) and impact of stress (p = 0.785). Using the PGIC exit interview that measured each patient’s impression of overall global change in symptoms and QOL these data also indicated overall significant improvements in symptoms and in satisfaction with the test supplement (moderately better improvements in symptoms and QOL or score of 4.8 ± 0.169, p 50 years) versus younger (TM natural dietary supplement safely and significantly reduced gastrointestinal symptoms and improved quality of life in subjects with a broad spectrum of gastrointestinal disorders and symptoms.

Introduction: Rosacea is a chronic skin condition affecting nearly 18% of the population worldwide. It is characterised by flushing or redness of the cheeks, nose, chin and/or forehead. In severe cases visible blood vessels, inflammatory acne or skin thickening may be present. The cause of rosacea remains unknown and treatments are limited. Emerging evidence suggests a link between gastrointestinal (GI) microbiome dysbiosis and rosacea. Here, we report 2 cases who received fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) and reported an improvement in concomitant rosacea. Case Description/Methods: Case 1: A female (65yrs) presented with known IBS characterised by bloating, abdominal pain and diarrhoea. Medical history included subtotal hysterectomy and optical rosacea, treated with hourly eye drops and cyclosporine eye gel. The patient was subsequently treated with vancomycin and rifaximin, with reduction in abdominal pain, bloating and bowel frequency. The patient also reported reduced eye irritation from optical rosacea. The patient then underwent FMT for 10 days (1 colonoscopic infusion, 9 rectal enemas). At 6 months, the patient reported a 75% improvement in GI symptoms and reported ongoing improvement in optical rosacea although still reliant on cyclosporine eye gel. Follow up at one year post FMT demonstrated recurrence of GI symptoms and optical rosacea. Case 2: A female (45yrs) presented with abdominal cramps, bloating, flatulence and alternating diarrhoea and constipation. Concomitant medical history was endometriosis and severe acne rosacea treated with twice daily application of topical mupirocin ointment. Investigations excluded organic pathology and IBS was diagnosed. The patient was subsequently treated with vancomycin and rifaximin followed by FMT for 10 days (1 colonoscopic infusion, 9 rectal enemas). At 6 months, the patient had no ongoing GI symptoms and continued to report ongoing improvement in acne rosacea with some flushing persisting. Follow up at 6 years post FMT demonstrated ongoing clinical improvement with occasional abdominal pain and diarrhoea. The patient no longer experienced acne rosacea and had ceased all medications. Discussion: To our knowledge this is the first report of antibiotics followed by FMT to treat rosacea, with improvements reported in both the short and long term. Future prospective trials are required to confirm FMT as a treatment for rosacea.