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Review
. 2021 Sep 13;13(1):54.
doi: 10.1186/s13099-021-00448-y.

The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: a systematic review

Laila Al-Ayadhi  1   2 , Naima Zayed  3 , Ramesa Shafi Bhat  4 , Nadine M S Moubayed  5 , May N Al-Muammar  6 , Afaf El-Ansary  7
Affiliations
Review

The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: a systematic review

Laila Al-Ayadhi et al. Gut Pathog. .

Abstract

Background: Innovative research highlighted the probable connection between autism spectrum disorder (ASD) and gut microbiota as many autistic individuals have gastrointestinal problems as co-morbidities. This review emphasizes the role of altered gut microbiota observed frequently in autistic patients, and the mechanisms through which such alterations may trigger leaky gut.

Main body: Different bacterial metabolite levels in the blood and urine of autistic children, such as short-chain fatty acids, lipopolysaccharides, beta-cresol, and bacterial toxins, were reviewed. Moreover, the importance of selected proteins, among which are calprotectin, zonulin, and lysozyme, were discussed as biomarkers for the early detection of leaky gut as an etiological mechanism of ASD through the less integrative gut-blood-brain barriers. Disrupted gut-blood-brain barriers can explain the leakage of bacterial metabolites in these patients.

Conclusion: Although the cause-to-effect relationship between ASD and altered gut microbiota is not yet well understood, this review shows that with the consumption of specific diets, definite probiotics may represent a noninvasive tool to reestablish healthy gut microbiota and stimulate gut health. The diagnostic and therapeutic value of intestinal proteins and bacterial-derived compounds as new possible biomarkers, as well as potential therapeutic targets, are discussed.

Keywords: Autism; Diet; Gut microbiota; Leaky gut; Probiotics; Short-chain fatty acids; Zonulin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Role of impaired gut microbiota and leaky gut in the etiology of autistic features. Reduced abundance of probiotic bacteria together with the overgrowth of pathogenic bacteria and accumulation of their toxic metabolites are thought to induce leaky gut, release of pro-inflammatory cytokines, and the development of autistic features through the gut-brain axis
Fig. 2
Fig. 2
Relationship between leaky gut and ASD demonstrating the increase of calprotectin, soluble CD14 as co-receptor of LPS, and p-cresol as toxic bacterial metabolite together with the decrease of zonulin and occludin as predictive biomarkers of leaky gut in autistic patients
Fig. 3
Fig. 3
Interaction between diet, gut microbiota, and the brain. Healthy prebiotic food usually accompanied with healthy gut with higher growth of probiotics, while food such as gluten/ casein-rich, refined sugars, artificial sweeteners and others show alteration of the gut microbiota composition, leading to inflamed or leaky gut with subsequent changes in the behavior profile through the microbiota-gut-brain axis
See this image and copyright information in PMC

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