The Role of the Microbiome on Health and Disease

This month's Diagnostic Digest centres on the human microbiome, estimated to encompass 30-40 trillion micro-organisms, outnumbering the human body's approximately 30 trillion cells.

The microbiome profoundly affects the progression of various diseases, including metabolic, infectious, oncological, and neurological disorders. Metabolically, it influences energy homeostasis and glucose regulation, impacting obesity, type 2 diabetes, non-alcoholic fatty liver disease and hypertension. Infectiously, it can either offer a protective barrier against pathogens or, through dysbiosis, increase infection susceptibility. In oncology, microbiome interactions may alter cancer progression by modulating immune responses and inflammation. Neurologically, it affects brain function through the gut-brain axis, influencing cognitive processes, mood, and susceptibility to neurodegenerative diseases.

This multidimensional influence highlights the microbiome's critical role in health and disease. Although gut microbiota is considered a promising novel target for the treatment of metabolic diseases, it is also necessary to encourage further studies to provide more valuable data for guiding the application of gut microbiota on disease therapy in future.

Recent key publications

1) Infant microbes and metabolites point to childhood neurodevelopmental disorders. Cell 2024; 187:1853-1873.e1815. Ahrens AP, Hy?tyl?inen T, Petrone JR et al. Link to full article

This extensive longitudinal study provides robust evidence linking early-life exposures and microbiome biomarkers to subsequent neurodevelopmental disorder (ND) diagnoses across a diverse cohort of 16,440 Swedish children monitored for over two decades. By integrating data from detailed questionnaires, including prenatal factors and family histories, with biological assessments such as cord serum metabolome and infant microbiota, the research elucidates potential pathways of immunodysregulation and metabolic perturbations that contribute to ND. The findings, which highlight significant associations with both general and specific ND subtypes—including intellectual disability and autism—underscore the critical role of early detection and the potential for targeted interventions. This groundbreaking work not only advances the understanding of ND aetiology but also paves the way for pre-emptive strategies in clinical practice, making it essential reading for experts in the field.

2) Emerging clinical relevance of microbiome in cancer: promising biomarkers and therapeutic targets. Protein Cell 2024; 15:239-260. Dai JH, Tan XR, Qiao H, Liu N. Link to full article

The expanding field of cancer microbiome research has rapidly evolved, revealing the pivotal role of microbiota in the onset and progression of cancer, thus becoming integral to the development of novel diagnostic tools and therapeutic interventions. This review delves into the latest advancements, discussing the potential of tumour-associated microbiota as both diagnostic and prognostic biomarkers and exploring their complex interactions with conventional cancer treatments such as chemotherapy, radiotherapy, and immunotherapy. Additionally, it examines the influence of microbial factors on treatment outcomes and assesses the benefits and risks associated with microbial interventions in oncology. By providing a comprehensive overview of current applications and progress in the integration of microbiota into cancer clinical practice, this article is an invaluable resource for researchers and clinicians seeking to enhance therapeutic efficacy and precision in oncology.

3) Associations between host microbiome and inflammation suggest role for host microbiome in driving COVID-19 disease severity. Microbes Infect 2024; 26:105247. MacCann R, Ghosh TS, Garcia Leon AA et al. Link to full article

This research elucidates the intricate relationships between the microbiome, systemic inflammation, and the severity of COVID-19, employing a sophisticated analytical approach to dissect the microbial taxonomy and host inflammatory profiles in affected individuals. Through 16SrDNA analysis of stool samples and correlation with plasma inflammatory biomarkers, the study identifies distinct microbiome modules associated with varying degrees of disease severity, from mild to critical. Hierarchical clustering and principal component analysis further reveal that specific microbial profiles correlate strongly with pro-inflammatory and anti-inflammatory biomarker clusters, suggesting potential paths for intervention. By providing a nuanced understanding of how microbiome composition influences immune responses in COVID-19, this article serves as a crucial resource for researchers aiming to develop targeted therapies to mitigate the most severe impacts of the disease.

4) Role of intestinal flora in the development of nonalcoholic fatty liver disease in children. Microbiol Spectr 2024; 12:e0100623. Zhang J, Shi M, Zhao C et al. Link to full article

As the prevalence of non-alcoholic fatty liver disease (NAFLD) escalates among obese adolescents in China, understanding the underlying biological mechanisms becomes imperative. This study leverages advanced 16S rRNA and metagenomic sequencing techniques to scrutinise the faecal microbiome of Chinese children diagnosed with NAFLD, non-alcoholic steatohepatitis (NASH), and non-alcoholic fatty liver (NAFL), against a backdrop of healthy controls. By establishing correlations between microbiota compositions, NAFLD-related indexes, and metabolic pathways, the research uncovers significant associations, notably the inverse relationship between specific microbial populations and body mass index. This comprehensive analysis not only provides insights into the microbiological underpinnings of NAFLD in paediatric populations but also introduces a microbiota-based diagnostic model, highlighting its potential in clinical applications and therapeutic advancements.

5) Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease. Hurych J, Mascellani Bergo A, Lerchova T et al, J Crohns Colitis 2024. SYNLAB-affiliated research. Link to full article

Treatment with anti-TNFα antibodies alters the dysbiotic faecal bacteriome in Crohn's disease [CD] patients. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. The authors analysed the microbiomes of 530 stool samples from 121 children, by 16S sequencing. Bacteriome composition changed after anti-TNF treatment in children with CD whereas no significant changes in the bacteriome or metabolome were noted in anti-TNF-treated children with juvenile idiopathic arthritis. The results suggest that Our findings suggest that gut mucosal healing is responsible for the bacteriome, and metabolome changes observed in CD, rather than any general effect of anti-TNF treatment.

?

6) Prognostic Value of Gut Microbiome for Conversion from Mild Cognitive Impairment to Alzheimer's Disease Dementia within 4 Years: Results from the AlzBiom Study. Laske C, Müller S, Munk M et al, Int J Mol Sci 2024. SYNLAB-affiliated research. Link to full article

Changes in intestinal microbiome composition have been described in Alzheimer’s disease (AD) patients and in animal models. The authors had previously identified a specific intestinal microbiome signature that discriminates amyloid-positive AD patients from healthy controls and can be used as a diagnostic measure. However longitudinal data of the gut microbiome and knowledge about its prognostic significance are limited. This longitudinal study involved analysis by shotgun metagenomics of the intestinal microbiome in 49 mild cognitive impairment patients over a mean of 3.7 years; 27 MCI patients converted to AD dementia and 22 remained stable. Novel and stable gut microbiome algorithms were identified that could accurately predict progression to AD dementia in this cohort. A model including 24 genera yielded an AUROC of 0.87 at baseline or 0.95 at 4 years follow-up, which could be further improved by including clinical parameters (age, gender, BMI and APOE genotype).

?