Using multi-omics to delve into Parkinson's disease gut microbiome
Published in Microbiology and Neuroscience
Parkinson's Disease and the Gut Microbiome
Parkinson's disease (PD) is a neurodegenerative disorder affecting approximately 10 million people worldwide, with a steadily increasing incidence. Previous research has suggested a clear link between the gut microbiome and PD, particularly in patients with the "gut-first" subtype of the disease. In this context, we aimed to assess differences in the gut microbiome of PD patients compared to healthy controls (HC), and also to compare an early stage of PD—idiopathic REM sleep behavior disorder (iRBD)—with both PD and HC groups.
The design
In this study, we employed a multi-layered meta-omics approach, including metagenomics, meta-transcriptomics, meta-proteomics, and meta-metabolomics, to gain a deeper understanding of the gut microbiome in these individuals. We enrolled 46 healthy controls, 27 iRBD patients, and 49 PD patients, all with no recent history of antibiotic use or other known confounding factors.
How we did it
Given the vast number of potential features generated by a multi-omics approach, we chose to use meta-metabolomics as the primary driver of our statistical analysis. This decision was based on two factors: first, metabolomics data were not influenced by confounders, and second, metabolites represent one of the final outputs of microbiome activity. Through this approach, we identified several compounds—such as β-glutamate, bile acids, isovalerate & isobutyrate, and glycerol—that were differentially abundant in PD and iRBD patients compared to healthy controls. In addition, thanks to this approach we also simplified the statistical proceedings by reducing the amount of comparisons.
Chemotaxis, flagellar assembly and taxonomy.
Interestingly, β-glutamate remains poorly understood, with only one known enzyme capable of metabolizing it. To explore the potential functions associated with these metabolomic differences, we retrieved all KEGG orthologs (KOs) known to interact with the differentially present compounds and their related metabolites. This analysis revealed that many KOs were less expressed in PD patients, particularly those involved in chemotaxis and flagellar assembly (FA).
We observed a significant reduction in the expression of genes related to chemotaxis and flagellar assembly in the PD gut microbiome, with over 50% of these genes showing decreased expression in the PD group. Notably, these differences were not reflected in gene abundance or potential, suggesting that the microbial community retains the genetic capacity for these functions but no longer expresses them. We then investigated which microbial taxa were responsible for this decrease and found a complex picture: some bacterial clusters expressed FA genes predominantly in healthy controls, one cluster was specific to HC, and another expressed FA genes only in PD patients. This highlights the importance of identifying not just which functions are present, but which microbes are actively expressing them.
Function and Taxonomy: Both Matter
This study reinforces the importance of examining the functional activity of the gut microbiome, rather than focusing solely on its taxonomic composition. However, it also underscores that the identity of the microbes expressing specific functions is crucial and appears to be linked to disease status. We strongly believe that understanding microbiome functionality will be key to unraveling its role in disease and improving microbiome-targeted interventions. Reactivating or enhancing specific missing functions within a given microbiome may be the key to restoring balance and improving patient outcomes.
Related work
We published a little earlier a paper on the same cohort, but using a co-expression network on the ratio of meta-transcriptomic/metagenomics data. This approach led us to find a disrupted network in the gut microbiome of PD individuals and an apparent discontinuation of the cross-feeding between commensals. The paper can be found here: Very nice paper
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Oncobiome
This collection of papers delves into the burgeoning field of oncobiome research, exploring the intricate relationship between cancer and the microbiome. The oncobiome encompasses the diverse microbial communities residing in and on the human body, which influence cancer development, progression, and treatment responses. By examining these interactions, our aim is to unravel the complex mechanisms through which the microbiome impacts oncogenesis and therapeutic outcomes.
This compilation highlights cutting-edge research, offering insights into potential diagnostic markers and novel therapeutic strategies, thereby advancing our understanding of cancer biology and paving the way for innovative, microbiome-targeted cancer treatments.
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Microbiome and Reproductive Health
Microbiome is calling for submissions to our Collection on Microbiome and Reproductive Health.
Our understanding of the intricate relationship between the microbiome and reproductive health holds profound translational implications for fertility, pregnancy, and reproductive disorders. To truly advance this field, it is essential to move beyond descriptive and associative studies and focus on mechanistic research that uncovers the functional underpinnings of the host–microbiome interface. Such studies can reveal how microbial communities influence reproductive physiology, including hormonal regulation, immune responses, and overall reproductive health.
Recent advances have highlighted the role of specific bacterial populations in both male and female fertility, as well as their impact on pregnancy outcomes. For example, the vaginal microbiome has been linked to preterm birth, while emerging evidence suggests that gut microbiota may modulate reproductive hormone levels. These insights underscore the need for research that explores how and why these microbial influences occur.
Looking ahead, the potential for breakthroughs is immense. Mechanistic studies have the power to drive the development of microbiome-based therapies that address infertility, improve pregnancy outcomes, and reduce the risk of reproductive diseases. Incorporating microbiome analysis into reproductive health assessments could transform clinical practice and, by deepening our understanding of host–microbiome mechanisms, lay the groundwork for personalized medicine in gynecology and obstetrics.
We invite researchers to contribute to this Special Collection on Microbiome and Reproductive Health. Submissions should emphasize functional and mechanistic insights into the host–microbiome relationship. Topics of interest include, but are not limited to:
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