New multi-national study adds to evidence linking alterations of the gut microbiome to autism

Strong new evidence linking alterations of the gut microbiome to autism spectrum disorders (ASD) comes from a new multi-national study by James Morton and colleagues.

In the study, researchers in North America, South America, Europe, and Asia developed an algorithm to re-analyze 25 datasets containing information on autistic and neurotypical controls. The datasets included 10 microbiome datasets and 15 other datasets containing information on dietary patterns, products of cell metabolism, cytokine profiles, and human brain gene expression profiles. Within each dataset, the algorithm found the best-matched pairs of autistic and neurotypical individuals based on age and sex.

“Rather than comparing average cohort results within studies,” study coauthor Gaspar Taroncher-Oldenburg says, “we treated each pair as a single data point, and thus were able to simultaneously analyze over 600 ASD-control pairs corresponding to a de facto cohort of over 1,200 children.” This allowed them to reliably identify microbes that differed in abundance between individuals with ASD and neurotypical controls.

The researchers say their analysis identified autism-specific metabolic pathways associated with specific human gut microbes. These pathways correlated with brain gene expression changes, restrictive dietary patterns, and pro-inflammatory cytokine profiles seen in individuals with ASD. “We hadn’t seen this kind of clear overlap between gut microbial and human metabolic pathways in autism before,” Morton says.

He adds, “We were able to harmonize seemingly disparate data from different studies and find a common language with which to unite them. With this, we were able to identify a microbial signature that distinguishes autistic from neurotypical individuals across many studies.”

Importantly, the researchers detected an overlap between microbes associated with autism and those identified in a long-term fecal microbiota transplant study led by James Adams and Rosa Krajmalnik-Brown (see ARRI 2023, No. 1). Commenting on the findings, Krajmalnik-Brown (who was not involved in the current study) says, “Another set of eyes looked at this, from a different lens, and they validated our findings.”

Rob Knight, a co-author of the current study, says, “Before this, we had smoke indicating the microbiome was involved in autism, and now we have fire.”

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“Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles,” James T. Morton, Dong-Min Jin, Robert H. Mills, Yan Shao, Gibraan Rahman, Daniel McDonald, Qiyun Zhu, Metin Balaban, Yueyu Jiang, Kalen Cantrell, Antonio Gonzalez, Julie Carmel, Linoy Mia Frankiensztajn, Sandra Martin-Brevet, Kirsten Berding, Brittany D. Needham, María Fernanda Zurita, Maude David, Olga V. Averina, Alexey S. Kovtun, Antonio Noto, Michele Mussap, Mingbang Wang, Daniel N. Frank, Ellen Li, Wenhao Zhou, Vassilios Fanos, Valery N. Danilenko, Dennis P. Wall, Paúl Cárdenas, Manuel E. Baldeón, Sébastien Jacquemont, Omry Koren, Evan Elliott, Ramnik J. Xavier, Sarkis K. Mazmanian, Rob Knight, Jack A. Gilbert, Sharon M.Donovan, Trevor D. Lawley, Bob Carpenter, Richard Bonneau, and Gaspar Taroncher-Oldenburg, Nature Neuroscience, June 26, 2023 (free online). Address: Gaspar Taroncher-Oldenburg, gtaroncher@gmail.com.

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“New research clarifies connection between autism and the microbiome,” news release, Susan Reslewic Keatley, Simons Foundation, June 26, 2023.

This article originally appeared in Autism Research Review International, Vol. 36, No. 3, 2023