Melbourne School of Psychological Sciences - Theses
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ItemBugs and Brains: The Gut and Mental Health Study Characterising the gut microbiota in anxiety, depression, irritable bowel syndrome, and their comorbidity( 2021)Background: The community of microorganisms inhabiting the gastrointestinal tract, collectively known as the gut microbiota, is intimately involved in the maintenance of host health. Comprehensive characterisation of the gut microbiota may enable us to better understand conditions whose pathophysiologies remain poorly understood, including internalising mental health disorders (anxiety and depressive disorders) and irritable bowel syndrome (IBS). While existing research has sought to characterise the gut microbiota in these conditions, the two systematic reviews included within this thesis reveal that studies have failed to consider essential confounders, including age, dietary intake, medication use, biological sex, and body mass index. The inadequate consideration of IBS and internalising disorder co-occurrence was also highlighted. Accordingly, this thesis aimed to investigate the gut microbiota in medication-free females with either IBS or an internalising disorder, as well as females with comorbid IBS and anxiety/depression, whilst controlling for key covariates (age, dietary intake, body mass index). Study 1 aimed to compare the gut microbiota of females with IBS relative to controls, as well as compare microbial composition between the three major IBS subtypes (IBS-diarrhoea, IBS-constipation, IBS-mixed). Study 2 aimed to characterise the gut microbiota of females with an internalising mental health disorder relative to controls. Study 3 aimed to compare and contrast the gut microbiota of females with comorbid IBS and an internalising disorder to controls, as well as to participants with IBS or an internalising disorder separately. Method: This thesis includes 162 females, recruited as part of the Bugs and Brains Study, who belonged to one of four groups: i) 42 controls; ii) 36 participants with an internalising disorder (depressive/anxiety disorder), but no IBS; iii) 42 participants with IBS, but no internalising disorder and iv) 42 participants with both an internalising disorder and IBS. Participants completed comprehensive questionnaires, attended a clinical mental health interview, collected a stool sample, and had their anthropometrics measured within a 1-month period. The gut microbiota was estimated using 16S rRNA gene sequencing on an Illumina MiSeq platform (V4 hypervariable region). Sequences were pre-processed using QIIME2 and following the DADA2 denoising pipeline to produce amplicon sequence variants (ASVs). ASVs were taxonomically assigned against the SILVA database (v.138). Data analysis was performed using R (v.1.3.1073), with the packages phyloseq and picante (alpha diversity), vegan (beta diversity), ANCOM-BC and MaAsLin2 (differential abundance), and randomForest (random forests). Results: Comprehensive multivariate analyses revealed key similarities with regards to the gut microbiota in IBS and anxiety/depression relative to controls. Females with IBS or an internalising disorder tended to be enriched in bacterial species associated with inflammation (e.g., Proteobacteria, Parabacteroides, Alistipes), and participants with either condition harboured a lower relative abundance of immunoregulatory SCFA-producing bacteria relative to controls (e.g., Barnesiella, Bacteroides eggerthii, Lachnospira, Faecalibacterium). Moreover, both the anxiety/depression and IBS groups had higher relative abundances of species known to degrade the essential amino acid tryptophan (i.e., Alistipes). While similar findings were observed in participants with comorbid anxiety/depression and IBS, the gut microbiota composition in this group was heterogeneous, and alterations were not more pronounced than those observed in participants with either disorder separately. Of note, higher abundances of mucin-degrading bacterial taxa were observed in IBS-C and IBS-M relative to controls and the IBS-D group (e.g., Akkermansia muciniphila), suggesting this alteration may be a unique to constipation. Conclusion: This thesis presents a comprehensive characterisation of the gut microbiota in females with IBS, an internalising mental health disorder, and their comorbidity. Similar alterations in the gut microbiota composition relative to controls were identified in these conditions and were not driven by their comorbidity, as participants in the IBS group had no lifetime history of a mental health disorder, and participants in the anxiety/depression group had no lifetime history of IBS. The included studies have great strength in highlighting these findings independent of key confounding factors, including age, dietary intake, BMI, and host sex. Participants in this study were also medication-free and without relevant medical comorbidities. While these studies are well placed to examine the cross-sectional associations between gut bacteria with IBS and internalising disorders, future research should seek to integrate functional analyses and examine other microbial members of the gut microbiota. Longitudinal research designs that combine taxonomic and functional investigations will elucidate the true complexity of gut microbe interactions with host mental health and gastrointestinal functioning.