Changes in adaptive behavior, gut microbiota and fecal metabolites following an integrative intervention in children with autism spectrum disorder

Emerging research suggests a link between gut microbiota, gut-derived metabolites, and autism spectrum disorder (ASD)-related behaviors and gastrointestinal issues. However, the clinical effectiveness and potential interactions of integrative interventions remain poorly understood. This pilot study compared TABAM, an integrative treatment, with conventional therapy for adaptive behavior in children aged 3–7 years with ASD.

Participants received either TABAM or conventional therapy for 12 months. Adaptive behavior and autism symptom severity were assessed at baseline and follow-up using VABS-II and CARS2-ST. Stool samples were collected at both time points for gut microbiota profiling using 16 S rRNA amplicon sequencing and targeted metabolomics.

Sixteen of 22 enrolled children completed the study (TABAM n = 10; control n = 6). VABS-II scores improved within the TABAM group, but the change did not differ significantly between groups. In the TABAM group, fecal serotonin increased and citrulline decreased; fecal propionate showed a significant between-group difference, decreasing in the TABAM group relative to controls.

Other metabolite changes did not remain significant after correction for multiple comparisons. Gut microbiota beta diversity did not differ significantly between groups or over time, whereas the TABAM group was comparatively associated with the preservation of phylogenetic diversity, and some compositional changes, particularly an increase in Bifidobacterium. These exploratory findings suggest that TABAM may be associated with improvements in adaptive functioning and concurrent changes in gut microbiome composition and metabolite profiles, supporting larger studies to clarify its potential clinical benefit and explore possible gut-brain axis mechanisms.

We thank Mona Khateeb (Department of Psychology, Tel-Hai University of Kiryat Shmona and the Galilee, Israel) for her assistance with data collection. This research was supported by an internal research grant from the Research Authority of Tel-Hai University of Kiryat Shmona in the Galilee. The funding body had no role in the design of the study; collection, analysis, and interpretation of data; writing of the manuscript; or in the decision to submit the article for publication.

Department of Nutritional Sciences, Tel-Hai University of Kiryat Shmona and the Galilee, Kiryat Shmona, Israel Carmel Even, Lili Nimri, Snait Tamir & Faiga Magzal Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel Laboratory of Nutrition and Human Health, MIGAL Galilee Research Institute, Kiryat Shmona, Israel Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy Department of Pediatrics, Saint Vincent de Paul Hospital, Nazareth, Israel Jamil Andrawes, Ahmad Marie, Arij Mansour-Kassabri, Lili Nimri & Nael Elias Department of Psychology, Tel-Hai University of Kiryat Shmona and the Galilee, Kiryat Shmona, Israel Department of Biotechnology, Tel-Hai University of Kiryat Shmona and the Galilee, Kiryat Shmona, Israel Natural Compounds and Organic Synthesis Laboratory, Migal-Galilee Research Institute, Kiryat, 11016, Shmona, Israel The authors declare no competing interests. This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Saint Vincent De Paul French Hospital, Nazareth (IRB Number: 013-2023-SVH).