AutismPhase 2/3DSA/GVBNCT07450443
Role of the Gut Vascular Barrier and Microbiota in Autism Spectrum Disorders
A Phase 2/3 study testing PostbiotiX Comfort® in people with Autism and Autism Disorder, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in Italy.
Trial summary
Recent research links gut microbiota alterations to Autism Spectrum Disorders (ASD), a neurobiological condition with multifactorial bases. In some ASD patients, altered gut flora and increased intestinal permeability are observed, influencing the central nervous system's development and function. Read more about this study
- Who is it for?
- Ages 3 to 8 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism, Autism Disorder, Autism Spectrum Disorder (ASD)
- What is being tested?
- PostbiotiX Comfort®
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesItaly
- Study dates
- 21 Mar 2023to Dec 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 8 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Group 1 and 2:
- Diagnosis of ASD according to DSM-5 diagnostic criteria;
- Clinical neurological evaluation by child neurologist and neuropsychologist with administration of standardized instruments such as Autism Diagnostic Observation Schedule-2 (ADOS-2) and/or Autism Diagnostic Interview-Revised (ADI-R) to support diagnosis;
- Assessment of psychomotor or intellectual development (Griffiths Scales, Wechsler Scales, Leiter Scale)
- Assessment of the following symptoms in the past three months: constipation, diarrhea, abnormal stool consistency, abnormal stool smell, flatulence, abdominal pain, unexplained daytime irritability, and nighttime awakening, and abdominal tenderness. The degree of gastrointestinal disturbances will be quantified before recruitment using an Italian version of the GI Severity Index. A score of at least 2 in a single item of gastrointestinal symptoms (item 1-6) was required for entry into the symptomatic group.
- Signed informed consent for analysis of intestinal microbiota and metabolome and administration of nutraceutical therapy with PostbiotiX Comfort ®.
Show all 9Show fewer
- Group 3 Inclusion criteria
- Males or females aged between 3 and 8 years whit typical development and absence of gastrointestinal symtomps
- Signed informed consent for analysis of intestinal microbiota and metabolome
Who cannot join
- Group 1 and 2
- Children with syndromic ASD or defined genetic diseases;
- Subjects with significant health problems requiring surgical treatment or continuous medical; treatment;
- Severe gastrointestinal problems requiring immediate (life-threatening) treatment;
- Severely underweight/malnourished children;
- Use of medications that may affect biomarkers assessed, for example: antibiotics and/or pre-, probiotics within 1 month prior to enrollment.
- Group 3 exclusion criteria
- Participants with gastrointestinal problems requiring immediate (life-threatening) treatment, or with gastrointestinal symptoms such as chronic irregular bowel movements (constipation, diarrhea), encopresis, recurrent abdominal bloating and pain, gastroesophageal reflux and vomiting, or food aversion.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sara Bulgheroni contact
Italy2 sites, 2 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, MI, 20133
D'Arrigo Stefano, MD, + 39 02.2394, stefano.darrigo@istituto-besta.it
- Recruiting
IRCCS Humanitas Reasearch Hospital (ICH) Laboratory of Microbiota and Mucosal Immunology
Milan
Maria Rescigno, MD, 02 82245431, maria.rescigno@hunimed.eu
About this study
Official title: Role of the Gut Vascular Barrier and Microbiota in Autism Spectrum Disorders: Evaluation of Efficacy of Postbiotic-based Nutraceutical Treatment
Recent research links gut microbiota alterations to Autism Spectrum Disorders (ASD), a neurobiological condition with multifactorial bases. In some ASD patients, altered gut flora and increased intestinal permeability are observed, influencing the central nervous system's development and function. Chronic gastrointestinal (GI) symptoms are commonly associated with ASD and correlate with its severity. This non-pharmacological interventional clinical study aims to investigate the role of gut microbiota on ASD and the effectiveness of postbiotic-based dietary supplements in children aged 3-8 years old. Gastrointestinal symptoms, behavioral profile and analysis of intestinal metagenomic and metabolomic profiles will be assessed before and after one-month treatment. The results of the study could enhance understanding of non-pharmacological therapeutic approaches in ASD and improve clinical management strategies and the behavioural functioning for children with ASD.
Read the detailed description
Modulating the microbiota could be an effective way to improve gastrointestinal issues and related behavioral symptoms in children with ASD, offering new treatment avenues. There is particular interest in alternatives to fecal microbiota transplantation, such as postbiotic supplements, which contain molecules naturally released during microbiota metabolism.
These molecules can regulate intestinal homeostasis and microbe-host interactions generating health benefits, possess anti-inflammatory and immunomodulatory activities, and contribute to the barrier activity of the intestinal epithelium. In line with findings for other nutraceutical therapies, dietary supplementation with postbiotics could resolve bowel problems in children with ASD and have positive consequences on behavioral regulation; however, the data collected in the literature is still scarce and limited to studies on mouse models of ASD.
This non-pharmacological clinical study, part of a collaboration between Fondazione IRCCS Istituto Neurologico Carlo Besta (FINCB) and Istituto Clinico Humanitas (ICH), evaluates postbiotic-based supplements' impact on gut microbiota's role in ASD.
Stool samples will be collected from patients at FINCB and FDG, and transported to ICH for analysis of the intestinal bacterial community and intestinal permeability. Participants will then receive a postbiotic-based dietary supplement. After treatment, changes in bowel habits, intestinal bacteria characteristics, intestinal permeability, and any behavioral changes will be evaluated.
Existing literature highlights the protective effects of postbiotics derived from Lactobacillus paracasei CNCM I-5220 on the intestine, specifically contributing to the maintenance of intestinal barrier integrity and protection against leaky gut syndrome.
Unlike probiotics, it provides immediate benefits without live bacteria risks, offering a safe alternative for fragile populations. PostbiotiX Comfort®, which includes the same fermented FOS by L. paracasei found in various infant food supplements (such as Smart D3 Matrix, Polivit Immuno Matrix, and Idra Matrix), will be utilized in this study. These products have been safely used in other formulations without any recorded safety concerns and have demonstrated an excellent toxicological profile.
- Conditions
- Autism, Autism Disorder, Autism Spectrum Disorder (ASD)
- Being tested
- PostbiotiX Comfort®, Control
- Keywords
- Autism Spectrum Disorders (ASD), Microbiota, Gastrointestinal symptoms, Behaviour regulation, Sensory profile
- Medical subject headings
- Autistic Disorder, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PostbiotiX Comfort®Dietary supplement
Treatment with a postbiotic dietary supplement, PostbiotiX Comfort®, administered for 1 month in participants from Group 1 and Group 2.
ControlOther
Participants in Group 3 do not receive any treatment.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (ASD with gastrointestinal symptoms): | Other | 30 patients with Autism Spectrum Disorder and coexisting gastrointestinal disorders, aged 3 to 8 years (male or female) Receives: Dietary Supplement: PostbiotiX Comfort® |
| Group 2 (ASD without gastrointestinal symptoms) | Other | 30 participants with Autism Spectrum Disorder without gastrointestinal disorders, aged 3 to 8 years (male or female) Receives: Dietary Supplement: PostbiotiX Comfort® |
| Group 3 (Typically developing) | Other | 30 participants with typical neurodevelopment and no gastrointestinal symptoms, aged 3 to 8 years (male or female) Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modulation of Gastrointestinal Symptoms in ASD with Postbiotic Supplement
The presence of gastrointestinal symptoms will be assessed at recruitment (T0) using the GI Severity Index.
Subjects recruited will be treated with the postbiotic-based dietary supplement, PostbiotiX Comfort®, once daily for 1 month.
The GI Severity Index will be repeated within one week after the end of the treatment (T1) to quantify changes in bowel regulation and one month after the end of the treatment (T2) to assess the stability of the observed changes.
Measured: 24 months
Secondary outcomes (7)
Effects of postbiotics on sleep regulation
Standardized behavioral assessments will be conducted through parents/caregivers reported questionnaires to evaluate the effects of postbiotic supplementation on sleep regulation. Sleep disturbances will be assessed through validated instruments designed to investigate difficulties related to sleep onset and maintenance, respiratory sleep disturbances, disorder of arousal, wake-sleep transition, excessive daytime sleepiness, and nocturnal hyperhidrosis.
Sleep regulation will be assessed using the italian version of the Sleep Disturbance Scale for Children. The scale consists of 26 items rated on a 5-point Likert scale (1 = never; 2 = occasionally; 3 = sometimes; 4 = often; 5 = always). The total raw score ranges from 26 to 130, with higher scores indicating greater severity of sleep disturbances.
Assessments will be conducted at three time points: baseline (T0), at enrollment in the interventional study; post-treatment (T1), within one week after the end of treatment; and follow-up (T
Measured: 24 months
Effects of postbiotics on behavioral regulation
Standardized behavioral assessments will be conducted through parents/caregivers reported questionnaires to evaluate the effects of postbiotic supplementation on behavioral regulation. Emotional and behavioral regulation will be assessed through validated instruments designed to investigate the presence and severity of emotional and behavioral problems, including internalizing and externalizing symptoms.
Behavioral and emotional problems will be assessed using the Italian versions of the Child Behavior Checklist (CBCL) according to age. The instrument consists of items rated on a 3-point Likert scale (0 = not true; 1 = somewhat or sometimes true; 2 = very true or often true). Higher scores indicate greater severity of emotional and behavioral problems. Raw scores will be converted into standardized T-scores (mean = 50, standard deviation = 10).
Assessments will be performed at three time points: baseline (T0), at enrollment in the interventional study; post-treatment (T1)
Measured: 24 months
Effects of postbiotics on sensory profile
Standardized behavioral assessments will be conducted through parents/caregivers reported questionnaires to evaluate the effects of postbiotic supplementation on sensory profile.
The sensory profile will be assessed using the Sensory Profile-2 (Italian version), completed by parents/caregivers for children aged 3-8 years. The questionnaire evaluates sensory functioning, self-regulation behavioral responses and the frequency of behavioral responses to environmental sensory stimuli. Raw scores are calculated for each sensory domain; higher scores indicate greater deviation from typical sensory processing patterns.
Assessments will be performed at three time points: baseline (T0), at enrollment in the interventional study; post-treatment (T1), within one week after the end of treatment; and follow-up (T2), within one month after the end of treatment to assess the stability of the observed changes. All questionnaires completed by the parents/caregivers will subsequently be discussed with
Measured: 24 months
Metagenomic analyses in typically developing children and in ASD before and after postbiotic treatment
Fecal samples obtained from control subjects and children with ASD with and without gastrointestinal symptoms. For the latter group, samples will be collected both prior to the initiation of supplement therapy (T0) and after treatment (T1).
Taxonomic and functional profiling of the fecal microbiota will be performed using shallow shotgun metagenomic sequencing. Total bacterial DNA will be extracted from fecal samples and sequenced using Illumina platforms. Taxonomic analyses will be performed at Species-level Genome Bin (SGB) resolution (8th taxonomic rank). Functional analyses will be based on destratified gene family and metabolic pathway abundances, with pathway annotation performed against the MetaCyc database. Differential abundance analyses (DAAs) will be performed on taxonomic profiles expressed as relative abundances and on gene family and pathway profiles normalized to copies per million (CPM) Unit of measure: Relative abundance of bacterial taxa (%)
Measured: 24 months
Metabolomic analyses in typically developing children and in ASD before and after postbiotic treatment
The following laboratory tests will be performed on fecal samples obtained from control subjects and children with ASD with and without gastrointestinal symptoms. For the latter group, samples will be collected both prior to the initiation of supplement therapy (T0) and after treatment (T1). Untargeted metabolomic analysis will be performed on fecal samples to identify metabolites of bacterial origin. Metabolites will be detected and quantified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), followed by bioinformatic analysis.
Unit of measure:
- Relative or absolute metabolite abundance (normalized peak intensity/concentration)
Measured: 24 months
Intestinal permeability analyses in typically developing children and in ASD before and after postbiotic treatment
The following laboratory tests will be performed on fecal samples obtained from control subjects and children with ASD with and without gastrointestinal symptoms. For the latter group, samples will be collected both prior to the initiation of supplement therapy (T0) and after treatment (T1). Intestinal permeability will be assessed by quantifying fecal levels of zonulin and albumin using commercially available enzyme-linked immunosorbent assays (ELISA). Increased fecal zonulin levels will be interpreted as indicative of tight junction disassembly and increased epithelial permeability. Elevated fecal albumin concentrations will be interpreted as a marker of intestinal barrier dysfunction associated with inflammatory leakage across the intestinal mucosa . Both biomarkers will be analyzed as indicators of altered intestinal permeability and gut barrier integrity.
Unit of measure:
- Zonulin family peptides: concentration (e.g., ng/mL or ng/g of feces)
- Albumin: concentration (e.g., ng/mL
Measured: 24 months
Investigation of the relationships between metagenomic/metabolomic profiles and behavioral/GI outcomes in children with ASD
Correlation analyses will be performed to investigate the relationships between metagenomic and metabolomic profiles and behavioral and gastrointestinal outcomes in children with ASD. This initial analysis will enable the identification of significant associations between microbial diversity, metabolite abundance, and clinical measures potentially modulated by postbiotic treatment.
Metagenomic, metabolomic, and intestinal permeability data will then be integrated with behavioral outcomes using advanced computational multi-omics approaches. Following data normalization and harmonization through standardized pipelines, metagenomic and metabolomic datasets will be combined using network-based integration strategies and multivariate methods, including Canonical Correlation Analysis (CCA), sparse Partial Least Squares (sPLS), and Multi-Omics Factor Analysis (MOFA), to identify shared functional signatures, key microbial-metabolic interactions, and convergent pathways across datasets.
Cross
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2026
- Study start21 Mar 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for AutismStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A total of 90 subjects will be enrolled in the study, including 60 children diagnosed with Autism Spectrum Disorder (ASD) and 30 typically developing children, aged 3 to 8 years. The 60 ASD patient with diagnosis of ASD will be devided into two groups (n= 30 per group) based on the presence or absence of gastrointestinal symptoms. Only participants in the ASD groups will receive the treatment with pstbiotic. The postbiotic, derived from the fermentation of Lactobacillus paracasei CNCM I-5220 and contained in PostbiotiX Comfort®, is a safe product that does not contain live or dead microorganisms, or any parts of them, but only the metabolic products of the microorganisms. The postbiotic supplement, PostbiotiX Comfort®, has a safety profile and is already available on the Italian market. Each participant will receive one sachet (4 g) of PostbiotiX Comfort® per day for a period of 30 consecutive days.
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Istituto Clinico Humanitas
- Responsible party
- Sponsor
- Investigators
- Stefano D'Arrigo, MD, Principal investigator, Fondazione IRCCS Istituto Neurologico Carlo Besta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07450443
- Sponsor's protocol ID
- DSA/GVB
- Acronym
- DSA/GVB
- Status last verified
- Jan 2026
- First submitted
- 19 Jan 2026
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994 Oct;24(5):659-85. doi: 10.1007/BF02172145.
PubMed 7814313Althoff RR. Dysregulated children reconsidered. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):302-5. No abstract available.
PubMed 20410722Bruni O, Ottaviano S, Guidetti V, Romoli M, Innocenzi M, Cortesi F, Giannotti F. The Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J Sleep Res. 1996 Dec;5(4):251-61. doi: 10.1111/j.1365-2869.1996.00251.x.
PubMed 9065877Chaidez V, Hansen RL, Hertz-Picciotto I. Gastrointestinal problems in children with autism, developmental delays or typical development. J Autism Dev Disord. 2014 May;44(5):1117-27. doi: 10.1007/s10803-013-1973-x.
PubMed 24193577Zagato E, Mileti E, Massimiliano L, Fasano F, Budelli A, Penna G, Rescigno M. Lactobacillus paracasei CBA L74 metabolic products and fermented milk for infant formula have anti-inflammatory activity on dendritic cells in vitro and protective effects against colitis and an enteric pathogen in vivo. PLoS One. 2014 Feb 10;9(2):e87615. doi: 10.1371/journal.pone.0087615. eCollection 2014.
PubMed 24520333Tsilingiri K, Rescigno M. Postbiotics: what else? Benef Microbes. 2013 Mar 1;4(1):101-7. doi: 10.3920/BM2012.0046.
PubMed 23271068Tsilingiri K, Rescigno M. Should probiotics be tested on ex vivo organ culture models? Gut Microbes. 2012 Sep-Oct;3(5):442-8. doi: 10.4161/gmic.20885. Epub 2012 Jun 20.
PubMed 22713266Tsilingiri K, Barbosa T, Penna G, Caprioli F, Sonzogni A, Viale G, Rescigno M. Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. Gut. 2012 Jul;61(7):1007-15. doi: 10.1136/gutjnl-2011-300971. Epub 2012 Feb 1.
PubMed 22301383Mileti E, Matteoli G, Iliev ID, Rescigno M. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLoS One. 2009 Sep 16;4(9):e7056. doi: 10.1371/journal.pone.0007056.
PubMed 19756155Pardridge WM. Blood-brain barrier delivery. Drug Discov Today. 2007 Jan;12(1-2):54-61. doi: 10.1016/j.drudis.2006.10.013. Epub 2006 Nov 13.
PubMed 17198973Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, Korecka A, Bakocevic N, Ng LG, Kundu P, Gulyas B, Halldin C, Hultenby K, Nilsson H, Hebert H, Volpe BT, Diamond B, Pettersson S. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014 Nov 19;6(263):263ra158. doi: 10.1126/scitranslmed.3009759.
PubMed 25411471Bertocchi A, Carloni S, Ravenda PS, Bertalot G, Spadoni I, Lo Cascio A, Gandini S, Lizier M, Braga D, Asnicar F, Segata N, Klaver C, Brescia P, Rossi E, Anselmo A, Guglietta S, Maroli A, Spaggiari P, Tarazona N, Cervantes A, Marsoni S, Lazzari L, Jodice MG, Luise C, Erreni M, Pece S, Di Fiore PP, Viale G, Spinelli A, Pozzi C, Penna G, Rescigno M. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell. 2021 May 10;39(5):708-724.e11. doi: 10.1016/j.ccell.2021.03.004. Epub 2021 Apr 1.
PubMed 33798472Grander C, Grabherr F, Spadoni I, Enrich B, Oberhuber G, Rescigno M, Tilg H. The role of gut vascular barrier in experimental alcoholic liver disease and A. muciniphila supplementation. Gut Microbes. 2020 Nov 9;12(1):1851986. doi: 10.1080/19490976.2020.1851986.
PubMed 33382359Sorribas M, Jakob MO, Yilmaz B, Li H, Stutz D, Noser Y, de Gottardi A, Moghadamrad S, Hassan M, Albillos A, Frances R, Juanola O, Spadoni I, Rescigno M, Wiest R. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis. J Hepatol. 2019 Dec;71(6):1126-1140. doi: 10.1016/j.jhep.2019.06.017. Epub 2019 Jul 8.
PubMed 31295531Mouries J, Brescia P, Silvestri A, Spadoni I, Sorribas M, Wiest R, Mileti E, Galbiati M, Invernizzi P, Adorini L, Penna G, Rescigno M. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol. 2019 Dec;71(6):1216-1228. doi: 10.1016/j.jhep.2019.08.005. Epub 2019 Aug 13.
PubMed 31419514
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Gut Vascular Barrier and Microbiota in Autism Spectrum Disorders: Evaluation of Efficacy of Postbiotic-based Nutraceutical Treatment
- ClinicalTrials.gov ID
- NCT07450443
- Acronym / sponsor ID
- DSA/GVB / DSA/GVB
- Conditions
- Autism, Autism Disorder, Autism Spectrum Disorder (ASD)
- Keywords
- Autism Spectrum Disorders (ASD), Microbiota, Gastrointestinal symptoms, Behaviour regulation, Sensory profile
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Collaborators
- Istituto Clinico Humanitas
- Study start
- 21 Mar 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 4 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent research links gut microbiota alterations to Autism Spectrum Disorders (ASD), a neurobiological condition with multifactorial bases. In some ASD patients, altered gut flora and increased intestinal permeability are observed, influencing the central nervous system's development and function. Chronic gastrointestinal (GI) symptoms are commonly associated with ASD and correlate with its severity. This non-pharmacological interventional clinical study aims to investigate the role of gut microbiota on ASD and the effectiveness of postbiotic-based dietary supplements in children aged 3-8 years old. Gastrointestinal symptoms, behavioral profile and analysis of intestinal metagenomic and metabolomic profiles will be assessed before and after one-month treatment. The results of the study could enhance understanding of non-pharmacological therapeutic approaches in ASD and improve clinical management strategies and the behavioural functioning for children with ASD.
Detailed description
Modulating the microbiota could be an effective way to improve gastrointestinal issues and related behavioral symptoms in children with ASD, offering new treatment avenues. There is particular interest in alternatives to fecal microbiota transplantation, such as postbiotic supplements, which contain molecules naturally released during microbiota metabolism.
These molecules can regulate intestinal homeostasis and microbe-host interactions generating health benefits, possess anti-inflammatory and immunomodulatory activities, and contribute to the barrier activity of the intestinal epithelium. In line with findings for other nutraceutical therapies, dietary supplementation with postbiotics could resolve bowel problems in children with ASD and have positive consequences on behavioral regulation; however, the data collected in the literature is still scarce and limited to studies on mouse models of ASD.
This non-pharmacological clinical study, part of a collaboration between Fondazione IRCCS Istituto Neurologico Carlo Besta (FINCB) and Istituto Clinico Humanitas (ICH), evaluates postbiotic-based supplements' impact on gut microbiota's role in ASD.
Stool samples will be collected from patients at FINCB and FDG, and transported to ICH for analysis of the intestinal bacterial community and intestinal permeability. Participants will then receive a postbiotic-based dietary supplement. After treatment, changes in bowel habits, intestinal bacteria characteristics, intestinal permeability, and any behavioral changes will be evaluated.
Existing literature highlights the protective effects of postbiotics derived from Lactobacillus paracasei CNCM I-5220 on the intestine, specifically contributing to the maintenance of intestinal barrier integrity and protection against leaky gut syndrome.
Unlike probiotics, it provides immediate benefits without live bacteria risks, offering a safe alternative for fragile populations. PostbiotiX Comfort®, which includes the same fermented FOS by L. paracasei found in various infant food supplements (such as Smart D3 Matrix, Polivit Immuno Matrix, and Idra Matrix), will be utilized in this study. These products have been safely used in other formulations without any recorded safety concerns and have demonstrated an excellent toxicological profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- A total of 90 subjects will be enrolled in the study, including 60 children diagnosed with Autism Spectrum Disorder (ASD) and 30 typically developing children, aged 3 to 8 years. The 60 ASD patient with diagnosis of ASD will be devided into two groups (n= 30 per group) based on the presence or absence of gastrointestinal symptoms. Only participants in the ASD groups will receive the treatment with pstbiotic. The postbiotic, derived from the fermentation of Lactobacillus paracasei CNCM I-5220 and contained in PostbiotiX Comfort®, is a safe product that does not contain live or dead microorganisms, or any parts of them, but only the metabolic products of the microorganisms. The postbiotic supplement, PostbiotiX Comfort®, has a safety profile and is already available on the Italian market. Each participant will receive one sachet (4 g) of PostbiotiX Comfort® per day for a period of 30 consecutive days.
| Arm | Type | Receives |
|---|---|---|
| Group 1 (ASD with gastrointestinal symptoms): | Other | Dietary Supplement: PostbiotiX Comfort®30 patients with Autism Spectrum Disorder and coexisting gastrointestinal disorders, aged 3 to 8 years (male or female) |
| Group 2 (ASD without gastrointestinal symptoms) | Other | Dietary Supplement: PostbiotiX Comfort®30 participants with Autism Spectrum Disorder without gastrointestinal disorders, aged 3 to 8 years (male or female) |
| Group 3 (Typically developing) | Other | Other: Control30 participants with typical neurodevelopment and no gastrointestinal symptoms, aged 3 to 8 years (male or female) |
Who may qualify
- Ages
- 3 to 8 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Group 1 and 2:
- Diagnosis of ASD according to DSM-5 diagnostic criteria;
- Clinical neurological evaluation by child neurologist and neuropsychologist with administration of standardized instruments such as Autism Diagnostic Observation Schedule-2 (ADOS-2) and/or Autism Diagnostic Interview-Revised (ADI-R) to support diagnosis;
- Assessment of psychomotor or intellectual development (Griffiths Scales, Wechsler Scales, Leiter Scale)
- Assessment of the following symptoms in the past three months: constipation, diarrhea, abnormal stool consistency, abnormal stool smell, flatulence, abdominal pain, unexplained daytime irritability, and nighttime awakening, and abdominal tenderness. The degree of gastrointestinal disturbances will be quantified before recruitment using an Italian version of the GI Severity Index. A score of at least 2 in a single item of gastrointestinal symptoms (item 1-6) was required for entry into the symptomatic group.
Key exclusion criteria (8 listed)
- Group 1 and 2
- Children with syndromic ASD or defined genetic diseases;
- Subjects with significant health problems requiring surgical treatment or continuous medical; treatment;
- Severe gastrointestinal problems requiring immediate (life-threatening) treatment;
- Severely underweight/malnourished children;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PostbiotiX Comfort®Treatment with a postbiotic dietary supplement, PostbiotiX Comfort®, administered for 1 month in participants from Group 1 and Group 2. | Dietary supplement | Group 1 (ASD with gastrointestinal symptoms):, Group 2 (ASD without gastrointestinal symptoms) |
| ControlParticipants in Group 3 do not receive any treatment. | Other | Group 3 (Typically developing) |
Primary outcome
Modulation of Gastrointestinal Symptoms in ASD with Postbiotic Supplement
Time frame: 24 months
The presence of gastrointestinal symptoms will be assessed at recruitment (T0) using the GI Severity Index. Subjects recruited will be treated with the postbiotic-based dietary supplement, PostbiotiX Comfort®, once daily for 1 month. The GI Severity Index will be repeated within one week after the end of the treatment (T1) to quantify changes in bowel regulation and one month after the end of the treatment (T2) to assess the stability of the observed changes.
7 secondary outcomes
Effects of postbiotics on sleep regulation
Time frame: 24 months
Effects of postbiotics on behavioral regulation
Time frame: 24 months
Effects of postbiotics on sensory profile
Time frame: 24 months
Metagenomic analyses in typically developing children and in ASD before and after postbiotic treatment
Time frame: 24 months
Metabolomic analyses in typically developing children and in ASD before and after postbiotic treatment
Time frame: 24 months
Intestinal permeability analyses in typically developing children and in ASD before and after postbiotic treatment
Time frame: 24 months
Investigation of the relationships between metagenomic/metabolomic profiles and behavioral/GI outcomes in children with ASD
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Background: PubMed 7814313Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994 Oct;24(5):659-85. doi: 10.1007/BF02172145.
- Background: PubMed 20410722Althoff RR. Dysregulated children reconsidered. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):302-5. No abstract available.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sara Bulgheroni contact
Stefano D'Arrigo, MD principal investigator
Fondazione IRCCS Istituto Neurologico Carlo Besta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing PostbiotiX Comfort® in people with Autism and Autism Disorder, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stefano D'Arrigo, MD (+ 39 02.2394, stefano.darrigo@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modulation of Gastrointestinal Symptoms in ASD with Postbiotic Supplement (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07450443, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026; AzTrials last refreshed its copy on 8 Nov 2026.