Thursday, 14 February 2019

The gut microbiome and autism... so far (continued)

Building on other reviews of the peer-reviewed science literature looking at the intestinal microbiota in relation to autism (see here), the paper published by Feitong Liu and colleagues [1] provides an updated 'where we're at' position in relation to the "potential evidence for the characteristic dysbiosis of gut microbiota in ASD [autism spectrum disorder] patients compared with healthy controls (HCs)." Just before you say anything, those are the authors words not mine; I'm not a fan of the word 'patients' nor use of the term 'healthy control' to denote not autism - not autistic, but there you go.

Language use aside, the Liu paper covers quite a lot of the peer-reviewed science talking about gut bacteria and autism up to March 2018. Their systematic review took in data from 16 studies - human studies "that compared the composition of gut microbiota in ASD patients and HCs using culture-independent techniques." Researchers had also previously registered their intention to conduct this review as per their PROSPERO entry (see here).

So what did their systematic review reveal? Well, they talked about how most studies looked at the intestinal microbiota via the examination of stool samples, although a couple relied on gut biopsy samples instead. Coincidentally, I spotted a bit of an error in the Liu paper in relation to their study reference numbering in one of the results sections, and how the Luna study (see here) and Williams study (see here) which relied on biopsy samples were replaced by other 'stool as a sample media' studies in the Liu write-up. It's only a small point and doesn't detract from the paper overall. The included studies also covered various different populations in a geographic sense as well as taking into account a mix of participants (with autism) in terms of the presence of gastrointestinal (GI) issues and the use of 'special' diets. Indeed, we are told that: "As restricted diet is very common in ASD patients, we tried to extract the information of eating habit in ASD and control group." Yes it is common, and yes it can have sometimes very negative effects (see here). Finally, all the studies included for review were "identified and assessed as medium (6–7) to high (8) quality" suggesting that the data were pretty reliable in a methodological sense.

Some key points emerged: "Overall, the changed structure of gut bacterial community in terms of β-diversity was observed coherently in ASD patients compared with HCs." Beta-diversity basically translates into 'between samples diversity' and in this case represents autism vs. not-autism controls. Out of the 16 studies included in their systematic review, Liu et al reported that "ten studies analyzed β-diversity (unweighted UniFrac distance, weighted UniFrac distances, and Bray-Curtis)." Six of those 10 studies "consistently reported that the microbiota of ASD patients clustered significantly apart from that of HCs." Ergo, there is evidence - some evidence - that the gut microbiome is significantly 'different' in autism compared with not-autism in a group sense. Some evidence at least.

Also: "Consistently, ASD patients had elevated abundance of Proteobacteria rather than HCs. In addition, Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter were consistently decreased, while Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium were increased in ASD patients relative to HCs."  Bear also in mind that Liu et al talked about various other bacterial species that were, in individual studies, elevated or depressed in the groups with autism, and how important such information might be. Such bacterial changes in terms of diversity or individual species predominating might also have knock-on effects as a result of the different chemical messages that different bacteria produce. One example: "Bacteroides is an abundant genus at all ages, from infants to adults. It is the main producer of propionate in the gut, and the abundance of propionate in feces correlates strongly with the abundance of Bacteroides." It probably won't surprise you to hear that propionic acid (propionate) has also got some research history when it comes to autism (see here) and indeed, with caveats, continues to do so [2]. Other examples are included in the Liu paper, including the 'chemical of the moment', butyrate (butyric acid) (see here). This complements other recently published research [3] too. And let's not forget how such bacteria and their chemical messaging also has some important 'effects' on things like gut barrier function and gut immune function, as part of the 'new triad' when it comes to autism and the gut (see here).

"Microbiome reconstitution could be a potential therapy to ASD patients in future." That's another topic raised in the Liu study on how "remodeling gut microbiota with diet, antibiotics, prebiotics, probiotics, and FMT [fecal microbiota transplant]" could be an option. Actually the future is now, as a quick scour of the autism research literature shows that some of these options are already being / have been investigated (see here and see here for examples). We do need a lot more information on the hows-and-whys of such therapeutic options; importantly covering safety, effectiveness and maybe highlighting the possible mechanisms involved, but there is already existing literature in this area.

As well as highlighting some of the shortcomings of the current research literature discussing the intestinal microbiota and autism, the Liu study provides a nice overview of this topic as things currently (up to March 2018) stand. Whether such information can eventually be 'manipulated' to improve things like quality of life in the context of autism remains to be seen...

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[1] Liu F. et al. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Translational Psychiatry. 2019; 43.

[2] Shams S. et al. Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder. Dev Psychobiol. 2019 Jan 28.

[3] Wang M. et al. Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder. mSystems. 2019 Jan 29;4(1). pii: e00321-18.

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