Cleary, David

Golm, Dennis

Law, Alexandra

English

Alterations to the gut microbiome have been associated with cognitive development and psychopathology- possibly through a bivariate communication pathway between the gut and the brain.As transmission of maternal gut microbiota to the infant occurs during birth, prenatal health behaviours such as smoking may adversely affect the infant’s gut microbiome, and subsequently their developmental trajectory.Recently, the gut microbiome has been hypothesised to be altered in people with neurodevelopmental diagnoses (NDDs) such as attention deficit/hyperactivity disorder or autism. Given the high heritability of NDDs, these alterations may not necessarily be causal risk factors, but may modulate neurodevelopmental or gastrointestinal symptoms. The latter of which has shown to be increased in people with NDDs.We conducted three umbrella systematic reviews (PROSPERO: CFR42021292394) on the association between:Prenatal health behaviours and NDDs.Prenatal health behaviours and infant gut microbiome composition.NDDs and gut microbiome composition.We further cross-referenced results to examine the evidence for a developmental framework in which maternal prenatal health behaviours impact neurodevelopmental symptoms via alterations to the infant gut microbiome. We included (i) 44, (ii) 4 and (iii) 17 systematic reviews into the umbrella review. While robust associations between prenatal health behaviours and NDDs have been identified, little work has been conducted on the impact of infant gut microbiota. Most systematic reviews on NDDs and gut microbiome alterations focused on autism and support differences between autistic and non-autistic populations. Results however are heterogeneous with few replicated results across studies. Some emerging evidence supports the developmental framework

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  University of BirminghamThe interplay between prenatal health behaviours,neurodevelopmental diagnoses and alterations inthe gut microbiomeGolm, Dennis; Law, Alexandra; Cleary, DavidLicense:None: All rights reservedDocument VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Golm, D, Law, A & Cleary, D 2023, 'The interplay between prenatal health behaviours, neurodevelopmentaldiagnoses and alterations in the gut microbiome: an umbrella review', 56th Annual Meeting of the InternationalSociety for Developmental Psychobiology, Utrecht, Netherlands, 26/07/23 - 28/07/23.<https://www.xcdsystem.com/isdp/program/fl8EZVu/index.cfm?pgid=2892&sid=27201&abid=101482>Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•Users may freely distribute the URL that is used to identify this publication.•Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 19. Aug. 2023ResultsInclusion of studies on negative prenatal health behaviours & neurodevelopmental diagnoses or symptoms in offspring (i.e.,maternal smoking, diet, gestational weight gain or pre-pregnancy obesity, maternal stress). Inclusion of studies on  prenatal  health behaviours and the composition of the offspring’s gut microbiome.Inclusion of studies on NDDs and gut microbiome composition.MethodsThe search strategy was pre-registered on Prospero  (CFR42021292394) and can be accessed here:Inclusion criteria: Publication in a peer-reviewed journal, English abstract, systematic review with or without a meta-analysis,human participants.Specific criteria for the three domains:1.2.3. D.Golm@soton.ac.ukPrenatal Health Behaviours & NeurodevelopmentalDiagnoses/ SymptomsPrenatal Health Behaviours & Offspring Gut MicrobiomeCompositionPrenatal Health Behaviours & Offspring Gut MicrobiomeCompositionMost Consistent FindingsBifidobacteriumProteobacteriaStreptococcusDialisterFirmicutes/Bacteroidetes ratioBacteroidesClostridiumAutismLower abundance of:Higher abundance of:FaecalibacteriumOdoribacterEggerthellaBacteroides uniformisPrevotellaceaeADHDLower abundance of:Higher abundance of:Slightly lower alpha diversityLactobacillusBifidobacteriaBacteroidesObesity/ GWGStressLower abundance of:High-fat diet Lower abundance of:Overlap Autism and prenatalstress are associatedwith a lower abundanceof BifidobacteriaADHD: Pos. association, potentially larger  Autism: Pos association, but driven by case-control designs and lower quality studies.Subjective stress        for more severe experiences.        Familial confounding should be considered. Overlap Stress and obesity/  GWGare associated with  NDDs & gut microbialcomposition To conduct a systematic review of systematic reviews and meta-analyses across the three domains:Association between prenatal health behaviours and NDDsAssociation between prenatal health behaviours and offspring gut microbiome compositionAssociation of NDDs and gut microbiome composition To summarise the overlap between the three domains in a developmental framework. BackgroundNeurodevelopmental diagnoses (NDDs) include Autism and Attention Deficit/ Hyperactivity Disorder (ADHD).Recently, a role of the  gut microbiome in the aetiology of NDDs has been discussed due to its communication with the brainvia the immune system (Cenit, Sanz & Codoñer-France, 2017). In line with that, children with NDDs have a high prevalence ofgastrointestinal problems  (Mannion & Leader, 2014).Microbial colonisation of the infant gut by maternal gut microbes occurs during  birth (Korpela, 2021).The composition of the maternal microbiome can be impacted by health behaviours and lifestyle factors  such as smoking andstress (Conlon & Bird, 2014). Aims: 1.2.3.  The interplay between prenatal health behaviours, neurodevelopmental diagnoses and alterations in the gut microbiome: An umbrella reviewDennis Golm*, Alexandra Law* & David Cleary***University of Southampton, School of Psychology, Centre for Innovation in Mental Health, UK, **University of Birmingham, Microbiology and Infection, UKPreliminary conclusionThe umbrella systematic review is still in progress. Domain 1: There is a positive association between some prenatal health behaviours and NDDs. There is however a need forhigh-quality longitudinal studies that control for familial confounding.Domain 2:  Few replicated results across studies. Some factors examined in domain 1 have not been sufficiently examinedregarding their impact on offspring  gut microbiome composition.Domain 3: Convincing evidence for an association between NDDs and gut microbiome composition but with few replicatedfindings. Future studies should utilise metagenomic sequencing techniques that allow for an analysis of functional profiles (i.e.,shallow shotgun).  References Cenit, M. C., Sanz, Y., & Codoñer-Franch, P. (2017). Influence of gut microbiota on neuropsychiatric disorders.         World journal of gastroenterology, 23(30), 5486.Conlon, M. A., & Bird, A. R. (2014). The impact of diet and lifestyle on gut microbiota and human health.         Nutrients, 7(1), 17-44.Korpela, K. (2021). Impact of delivery mode on infant gut microbiota.         Annals of Nutrition and Metabolism, 77(Suppl. 3), 11-19.Mannion, A., & Leader, G. (2014). Gastrointestinal symptoms in autism spectrum disorder: A literature review.         Review Journal of   Autism and Developmental Disorders, 1, 11-17.Abstract screeningFull-text screeningIncludedDomain 1: 275Domain 2: 51Domain 3: 118Domain 1: 57 Domain 2:   6Domain 3: 27Domain 1: 44Domain 2:   4Domain 3: 17No effects for...Domain 2: No evidence for most maternal dietary factors. No evidence for a persistent alteration of the infant gut microbiome following the cessation of pro-/prebiotic supplementation.ADHD: Association with dimensional, but notcategorical measures.Autism: No evidence.ADHD: Positive association, potentially  due tofamilial confounding.Autism: Association may be stronger SmokingObesity/ GWG       for GWG, familial confounding        should be considered.

The interplay between prenatal health behaviours, neurodevelopmental diagnoses and alterations in the gut microbiome:an umbrella review

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The interplay between prenatal health behaviours, neurodevelopmental diagnoses and alterations in the gut microbiome:an umbrella review

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