Role of the Gut Vascular Barrier and Microbiota in Autism Spectrum Disorders

NCT07450443 | Recruiting Phase 2

• 1 other identifier: DSA/GVB
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Autism; Autism Disorder; Autism Spectrum Disorder (ASD)

Keywords

Autism Spectrum Disorders (ASD); Microbiota; Gastrointestinal symptoms; Behaviour regulation; Sensory profile

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months

Secondary Outcomes (7)

• Effects of postbiotics on sleep regulation

  24 months

• Effects of postbiotics on behavioral regulation

  24 months

• Effects of postbiotics on sensory profile

  24 months

• Metagenomic analyses in typically developing children and in ASD before and after postbiotic treatment

  24 months

• Metabolomic analyses in typically developing children and in ASD before and after postbiotic treatment

  24 months

Study Arms (3)

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)

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)

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)

Other: Control

Interventions

PostbiotiX Comfort® DIETARY_SUPPLEMENT

Treatment with a postbiotic dietary supplement, PostbiotiX Comfort®, administered for 1 month in participants from Group 1 and Group 2.

Group 1 (ASD with gastrointestinal symptoms):; Group 2 (ASD without gastrointestinal symptoms)

Control OTHER

Participants in Group 3 do not receive any treatment.

Group 3 (Typically developing)

Eligibility Criteria

• Age: 3 Years - 8 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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 ®.
• 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

You may not qualify if:

• 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.
• \- 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.

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead
• Istituto Clinico Humanitas: collaborator

Study Sites (2)

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, MI, 20133, Italy

RECRUITING

IRCCS Humanitas Reasearch Hospital (ICH) Laboratory of Microbiota and Mucosal Immunology

Milan, Italy

RECRUITING

Related Publications (37)

• 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.

  PMID: 7814313 BACKGROUND

• Althoff RR. Dysregulated children reconsidered. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):302-5. No abstract available.

  PMID: 20410722 BACKGROUND

• Bruni 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.

  PMID: 9065877 BACKGROUND

• Chaidez 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.

  PMID: 24193577 BACKGROUND

• Zagato 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.

  PMID: 24520333 BACKGROUND

• Tsilingiri K, Rescigno M. Postbiotics: what else? Benef Microbes. 2013 Mar 1;4(1):101-7. doi: 10.3920/BM2012.0046.

  PMID: 23271068 BACKGROUND

• Tsilingiri 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.

  PMID: 22713266 BACKGROUND

• Tsilingiri 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.

  PMID: 22301383 BACKGROUND

• Mileti 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.

  PMID: 19756155 BACKGROUND

• Pardridge 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.

  PMID: 17198973 BACKGROUND

• Braniste 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.

  PMID: 25411471 BACKGROUND

• Bertocchi 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.

  PMID: 33798472 BACKGROUND

• Grander 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.

  PMID: 33382359 BACKGROUND

• Sorribas 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.

  PMID: 31295531 BACKGROUND

• Mouries 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.

  PMID: 31419514 BACKGROUND

• Spadoni I, Zagato E, Bertocchi A, Paolinelli R, Hot E, Di Sabatino A, Caprioli F, Bottiglieri L, Oldani A, Viale G, Penna G, Dejana E, Rescigno M. A gut-vascular barrier controls the systemic dissemination of bacteria. Science. 2015 Nov 13;350(6262):830-4. doi: 10.1126/science.aad0135.

  PMID: 26564856 BACKGROUND

• Spadoni I, Fornasa G, Rescigno M. Organ-specific protection mediated by cooperation between vascular and epithelial barriers. Nat Rev Immunol. 2017 Dec;17(12):761-773. doi: 10.1038/nri.2017.100. Epub 2017 Sep 4.

  PMID: 28869253 BACKGROUND

• Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, Kelly DL, Cascella N, Fasano A. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016 Nov 29;7:49. doi: 10.1186/s13229-016-0110-z. eCollection 2016.

  PMID: 27957319 BACKGROUND

• Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008.

  PMID: 21248165 BACKGROUND

• Croonenberghs J, Wauters A, Devreese K, Verkerk R, Scharpe S, Bosmans E, Egyed B, Deboutte D, Maes M. Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism. Psychol Med. 2002 Nov;32(8):1457-63. doi: 10.1017/s0033291702006037.

  PMID: 12455944 BACKGROUND

• Esnafoglu E, Cirrik S, Ayyildiz SN, Erdil A, Erturk EY, Dagli A, Noyan T. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J Pediatr. 2017 Sep;188:240-244. doi: 10.1016/j.jpeds.2017.04.004. Epub 2017 May 11.

  PMID: 28502607 BACKGROUND

• Julio-Pieper M, Bravo JA, Aliaga E, Gotteland M. Review article: intestinal barrier dysfunction and central nervous system disorders--a controversial association. Aliment Pharmacol Ther. 2014 Nov;40(10):1187-201. doi: 10.1111/apt.12950. Epub 2014 Sep 28.

  PMID: 25262969 BACKGROUND

• Sharon G, Cruz NJ, Kang DW, Gandal MJ, Wang B, Kim YM, Zink EM, Casey CP, Taylor BC, Lane CJ, Bramer LM, Isern NG, Hoyt DW, Noecker C, Sweredoski MJ, Moradian A, Borenstein E, Jansson JK, Knight R, Metz TO, Lois C, Geschwind DH, Krajmalnik-Brown R, Mazmanian SK. Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell. 2019 May 30;177(6):1600-1618.e17. doi: 10.1016/j.cell.2019.05.004.

  PMID: 31150625 BACKGROUND

• Buffington SA, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016 Jun 16;165(7):1762-1775. doi: 10.1016/j.cell.2016.06.001.

  PMID: 27315483 BACKGROUND

• Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.

  PMID: 28122648 BACKGROUND

• Kang DW, Adams JB, Coleman DM, Pollard EL, Maldonado J, McDonough-Means S, Caporaso JG, Krajmalnik-Brown R. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019 Apr 9;9(1):5821. doi: 10.1038/s41598-019-42183-0.

  PMID: 30967657 BACKGROUND

• Ding HT, Taur Y, Walkup JT. Gut Microbiota and Autism: Key Concepts and Findings. J Autism Dev Disord. 2017 Feb;47(2):480-489. doi: 10.1007/s10803-016-2960-9.

  PMID: 27882443 BACKGROUND

• Iovene MR, Bombace F, Maresca R, Sapone A, Iardino P, Picardi A, Marotta R, Schiraldi C, Siniscalco D, Serra N, de Magistris L, Bravaccio C. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. 2017 Apr;182(3-4):349-363. doi: 10.1007/s11046-016-0068-6. Epub 2016 Sep 21.

  PMID: 27655151 BACKGROUND

• Fulceri F, Morelli M, Santocchi E, Cena H, Del Bianco T, Narzisi A, Calderoni S, Muratori F. Gastrointestinal symptoms and behavioral problems in preschoolers with Autism Spectrum Disorder. Dig Liver Dis. 2016 Mar;48(3):248-54. doi: 10.1016/j.dld.2015.11.026. Epub 2015 Dec 11.

  PMID: 26748423 BACKGROUND

• Mayer EA, Padua D, Tillisch K. Altered brain-gut axis in autism: comorbidity or causative mechanisms? Bioessays. 2014 Oct;36(10):933-9. doi: 10.1002/bies.201400075. Epub 2014 Aug 22.

  PMID: 25145752 BACKGROUND

• Afzal N, Murch S, Thirrupathy K, Berger L, Fagbemi A, Heuschkel R. Constipation with acquired megarectum in children with autism. Pediatrics. 2003 Oct;112(4):939-42. doi: 10.1542/peds.112.4.939.

  PMID: 14523189 BACKGROUND

• Wasilewska J, Klukowski M. Gastrointestinal symptoms and autism spectrum disorder: links and risks - a possible new overlap syndrome. Pediatric Health Med Ther. 2015 Sep 28;6:153-166. doi: 10.2147/PHMT.S85717. eCollection 2015.

  PMID: 29388597 BACKGROUND

• Niehus R, Lord C. Early medical history of children with autism spectrum disorders. J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S120-7. doi: 10.1097/00004703-200604002-00010.

  PMID: 16685178 BACKGROUND

• McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83. doi: 10.1542/peds.2013-3995.

  PMID: 24777214 BACKGROUND

• Vuong HE, Hsiao EY. Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder. Biol Psychiatry. 2017 Mar 1;81(5):411-423. doi: 10.1016/j.biopsych.2016.08.024. Epub 2016 Aug 26.

  PMID: 27773355 BACKGROUND

• Miles JH. Autism spectrum disorders--a genetics review. Genet Med. 2011 Apr;13(4):278-94. doi: 10.1097/GIM.0b013e3181ff67ba.

  PMID: 21358411 BACKGROUND

• Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009 Jun;65(6):591-8. doi: 10.1203/PDR.0b013e31819e7203.

  PMID: 19218885 BACKGROUND

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Stefano D'Arrigo, MD

  Fondazione IRCCS Istituto Neurologico Carlo Besta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefano D'Arrigo, MD

CONTACT

+ 39 02.2394; stefano.darrigo@istituto-besta.it

Sara Bulgheroni

CONTACT

sara.bulgheroni@istituto-besta.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: March 4, 2026
• Study Start: March 21, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)