DNA of Gut Bacteria Scores Hits in Autism?

[enorbet]

TL;DR

The powerful and apparently transferable effect of gut bacteria populations in autism. Is this real?

Greetings
Since genome sequencing is apparently having a major impact on medical science, just to name one field, I am interested in hearing/reading more about this recent event regarding autism. It seems to me this could have far-reaching implications and possibly major impact on how we view health. Here is the article I read but since it appeared in The economist I'd very much like to hear from people closer to the medical sciences

https://www.economist.com/science-a...nked-to-gut-bacteria?utm_source=pocket-newtab

 

[256bits]

There is probably a lot that is not known about gut bacteria IMO.
Hopefully the discussion in the Economist pans out.

 

[enorbet]

A net search today resulted in a more pointed, more thorough and scientific perspective.

https://www.medicalnewstoday.com/articles/321566.php
If you have interest don't miss the articles listed by links to the right, especially the CalTech item.

 

[Ygggdrasil]

There have been a few scientific papers published on the subject recently. Here's the paper published in the journal Scientific Reports being discussed by the Economist article:

Kang et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep 9: 5821 (2019) https://www.nature.com/articles/s41598-019-42183-0

Abstract:

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

Essentially, many individuals with autism experience gastrointestinal problems and show differences in their gut bacteria relative to normal individuals. This has led some to suggest that differences in gut bacteria could cause or contribute to autism (an alternative hypothesis would be that the gastrointestinal symptoms and differences in gut bacteria are a symptom of the underlying factors that cause autism).

To test this hypothesis, the authors performed fecal transplantation to replace the gut microbiomes of autistic individuals with more "normal" microbiomes, and two years after the treatment, the authors report improvements both in gastrointestinal symptoms and in symptoms related to autism. These results are promising and are consistent with the hypothesis that gut bacteria could contribute to autism, but more research is required. The study was fairly small (18 individuals) and the study lacked a control group to test for placebo effects.

This week, researchers at CalTech published a paper in the journal Cell that purports to provide much more direct evidence for a connection between gut bacteria and autism.

Sharon et al. Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell 177: 1600 https://doi.org/10.1016/j.cell.2019.05.004

Abstract:

Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.

They introduced gut bacteria from individuals with or without autism into laboratory mice then examined whether the mice with the exhibit behavioral symptoms consistent with autism. While the study got published in a high profile scientific journal, I have seen many scientists who are skeptical of the results. For example, the behavioral phenotypes (see Fig taken from the paper below) are generally small and are only visible in the second generation of mice after gut bacteria transplantation. The study is also based on a small number of human samples (most of the experiments are based on samples from three control individuals and five ASD individuals), and given that there are no generally accepted models of autism in mice, it is unclear how accurately changes in mouse behavior recapitulate autistic behavior. For example, given that individuals with autism experience gastrointestinal issues, could the observed behavioral changes merely reflect changes in gastrointestinal function and nutrition?

Here's an article critiquing the study, which makes some of the same points as I discussed above:
https://blogs.sciencemag.org/pipeline/archives/2019/05/31/autism-mouse-models-for-the-microbiome
While there is some evidence to suggest a connection between autism and gut bacteria, there is still more work that needs to be done to clearly establish the link and determine the mechanisms involved.

 

[member 656954]

Economist Radio's Babbage podcast had an interview with one of the researchers working on the potential autism / gut flora link late last month:

https://www.economist.com/podcasts/2019/08/21/gut-feeling-a-link-between-bacteria-and-autism