Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial

Luigi Mazzone; Sean W Dooling; Elisabetta Volpe; Mirko Uljarević; Jillian L Waters; Andrea Sabatini; Lucrezia Arturi; Roberta Abate; Assia Riccioni; Martina Siracusano; Marcela Pereira; Lars Engstrand; Fernanda Cristofori; Domenico Adduce; Ruggiero Francavilla; Mauro Costa-Mattioli; Antonio Y Hardan

doi:10.1016/j.chom.2023.11.021

Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial

Cell Host Microbe. 2024 Jan 10;32(1):106-116.e6. doi: 10.1016/j.chom.2023.11.021. Epub 2023 Dec 18.

Authors

Luigi Mazzone¹, Sean W Dooling², Elisabetta Volpe³, Mirko Uljarević⁴, Jillian L Waters⁵, Andrea Sabatini³, Lucrezia Arturi⁶, Roberta Abate⁷, Assia Riccioni⁶, Martina Siracusano⁸, Marcela Pereira⁹, Lars Engstrand⁹, Fernanda Cristofori¹⁰, Domenico Adduce¹⁰, Ruggiero Francavilla¹⁰, Mauro Costa-Mattioli¹¹, Antonio Y Hardan¹²

Affiliations

¹ Child Neurology and Psychiatry Unit, Department of Neurosciences, Policlinico Tor Vergata Foundation Hospital, Viale Oxford 81, 00133 Rome, Italy; Systems Medicine Department, University of Rome Tor Vergata, Montpellier Street 1, 00133 Rome, Italy. Electronic address: luigi.mazzone@ptvonline.it.
² Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX, USA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Altos Labs, Inc, Bay Area Institute of Science, Redwood City, CA 94065, USA.
³ Molecular Neuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy.
⁴ Melbourne School of Psychological Sciences, University of Melbourne, Tin Alley, Carlton, Melbourne, VIC 3010, Australia.
⁵ Altos Labs, Inc, Bay Area Institute of Science, Redwood City, CA 94065, USA.
⁶ Child Neurology and Psychiatry Unit, Department of Neurosciences, Policlinico Tor Vergata Foundation Hospital, Viale Oxford 81, 00133 Rome, Italy; Systems Medicine Department, University of Rome Tor Vergata, Montpellier Street 1, 00133 Rome, Italy.
⁷ Child Neurology and Psychiatry Unit, Department of Neurosciences, Policlinico Tor Vergata Foundation Hospital, Viale Oxford 81, 00133 Rome, Italy.
⁸ Child Neurology and Psychiatry Unit, Department of Neurosciences, Policlinico Tor Vergata Foundation Hospital, Viale Oxford 81, 00133 Rome, Italy; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Montpellier Street 1, 00133 Rome, Italy.
⁹ Centre for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Solna, Sweden.
¹⁰ Pediatric Gastroenterology and Hepatology Unit, Department of Interdisciplinary Medicine, Children's Hospital-Giovanni XXIII, University of Bari Aldo Moro, 70121 Bari, Italy.
¹¹ Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX, USA; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Altos Labs, Inc, Bay Area Institute of Science, Redwood City, CA 94065, USA. Electronic address: mcostamattioli@altoslabs.com.
¹² Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. Electronic address: hardanay@stanford.edu.

PMID: 38113884
DOI: 10.1016/j.chom.2023.11.021

Abstract

Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized across different measures. Interestingly, ATCC-PTA-6475, but not the parental strain of DSM-17938, reverses the social deficits in a preclinical mouse model for ASD. Collectively, our findings show that L. reuteri enhances social behavior in children with ASD, thereby warranting larger trials in which strain-specific effects should also be investigated.

Keywords: autism spectrum disorder; clinical trial; gut-microbiome-brain axis; probiotic; social behavior.

Publication types

Randomized Controlled Trial

MeSH terms

Animals
Autism Spectrum Disorder* / therapy
Autistic Disorder* / therapy
Child
Double-Blind Method
Humans
Mice
Social Behavior
Treatment Outcome