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Metatranscriptomics takes on the daunting task of unraveling the intricate relationships between humans and the trillions of microbial cells that reside inside and on them Asymphony of trillions of helpful and harmful microbial cells in the human microbiome create a delicate balance aiding in the health of individuals.1,2
“As our knowledge base around the microbiome grows, we continue to see its influence on both the onset of disease, including cancer, diabetes, and GI disorders like Crohn’s disease, as well as its effect on treatment outcomes,” said Matthew Hymes, infectious disease and microbiology segment manager at Illumina.
“Previously the focus was on identifying dysbiosis and understanding the proper balance of a microbiome whereas metatranscriptomics identifies how microorganisms complement each other and can at times supplant the absence of others and the metabolic processes they provide while also identifying organisms that are irreplaceable in the community.”
Influencing cancer development and therapy
The microbes that make up about 25 percent of the tumor environment in certain cancers can promote or block antitumor immunity.3 Four main mechanisms govern the link between the tumor microbiome and cancer: increased gene mutations directly promoting tumorigenesis, regulation of oncogenes or oncogenic pathways, modulation of the host immune system, and production of small molecules or metabolites that influence cancer development, progression, and therapeutic response.2
As an example, researchers at Fred Hutchinson Cancer Center demonstrated metabolically active bacterial members of the intratumoral microbiota in colorectal cancer (CRC). These bacteria along with malignant tumor cells interact with the commonly used, antimetabolite chemotherapeutic 5-fluorouracil (5-FU). In the highly complex interactions, bacterial community members appeared to be either overly sensitive to 5-FU, resistant, or resistant and depleting.4
In fact, to improve response to immunotherapies an emerging approach is priming patients with fecal microbial transfers (FMT)3. As illustrated in a recent Nature article, scientists are “exploring the role of diet and gut-microbe diversity, as well as revealing interactions between the organisms that reside in the gut and those that live in tumors themselves, potentially opening up new targets for treatment.”6
A dynamic relationship with the host
The gut microbiome can influence human health a nd affect physiology through its effect on pathogen resistance, gut barrier maintenance, metabolism, immunity, and neural signaling.6 For instance, butyrate is an important health-promoting bacterial metabolite with diverse beneficial properties, including its role in host energy metabolism6.
Individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex, debilitating disorder, display symptoms of severe fatigue and post-exertional malaise. Notably “long COVID” manifests as phenotypical abnormalities shared with ME/CFS.6
To probe the microbiome’s role in ME/CFS, the Jackson Laboratory and Bateman Horne Center performed a large-scale multiomics investigation integrating detailed clinical and lifestyle data, gut metagenomics, and plasma metabolomics in short- and long-term ME/CFS patients along with healthy controls.5
Findings showed that “short-term disease was characterized by greater gut microbial dysbiosis, particularly a depletion of butyrateproducing microbes while long-term disease was associated with more severe phenotypic and metabolic abnormalities.”5
A related metagenomics and metabolomics analysis from Columbia University Medical Center also revealed extensive gut microbiome dysbiosis in ME/CFS and found that reduced F. prausnitzii may contribute to butyrate deficiency and symptom severity.6
From birth onward
The early-life gut microbiome affects child growth through immune, metabolic, and endocrine pathways and could contribute to shunting, which affects one-in-five children globally.7
In results from a rural Zimbabwe study, taxonomic composition of the gut microbiome was poorly predictive of child growth. However, functional metagenomic features, particularly B-vitamin and nucleotide biosynthesis pathways, moderately predicted both attained linear and ponderal growth and growth velocity.7
This raises the intriguing possibility that altered succession and assembly of the infant gut microbiome may drive some of the poorer clinical outcomes in children who are HIV exposed but uninfected.7
Utilizing the power of metatranscriptomics allows researchers to identify both who is present at a microorganismal level, and, more importantly, what role these organisms play in the microbial community and how they affect the surrounding environment.
- Looi MK. The human microbiome: Everything you need to know about the 39 trillion microbes that call our bodies home. BBC Science Focus. Published: 14th July, 2020
- Chen Y, Wu F-H, Wu P-Q et al. The Role of the Tumor Microbiome in Tumor Development and Its Treatment. Front. Immunol. 2022; 13:935846. DOI: 10.3389/fimmu.2022.935846
- Erdmann J. How gut bacteria could boost cancer treatments. Nature 2022; 607: 436–439. DOI: 10.1038/d41586-022-01959-7.
- LaCourse KD, Zepeda-Rivera M, Kempchinsky AG et al. The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota, Cell Reports. 2022; Vol. 41, Issue 7. DOI: 10.1016/j.celrep.2022.111625.
- Xiong R, Gunter C, Fleming E et al. Multi-’omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients. Cell Host Microbe. 2023 Feb 8; 31(2):273-287.e5. DOI: 10.1016/j.chom.2023.01.001.
- Guo C, Che X, Briese T et al. Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host Microbe. 2023 Feb 8;31(2):288-304.e8. DOI: 10.1016/j.chom.2023.01.004.
- Robertson RC, Edens TJ, Carr L et al. The gut microbiome and early-life growth in a population with high prevalence of stunting. Nat Commun. 2023; 14, 654. DOI:10.1038/s41467-023-36135-6
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