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Microbes & Immunity Microbial involvement in ME/CFS

Numerous underlying biological irregularities have been to a decrease in gastrointestinal diseases. The human
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recognized in subjects with ME/CFS, as exemplified by virome is mainly composed of bacteriophages, and the
impaired energy metabolism, mitochondrial dysregulation, role that they play in the gut is related to modulating the
gastrointestinal and redox imbalances, altered immune bacteriome. Typical microorganisms in the human gut
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processes (including autoimmune response), sleep are represented by approximately 100 bacterial species
disturbances, and multiple central and autonomic nervous that belong to the following eight phyla: Actinomycetota,
system abnormalities. 5,6 Bacillota, Bacteroidota, Campylobacterota, Fusobacteriota,

Nevertheless, not all patients experience the same Pseudomonadota, Thermodesulfobacteriota, and
clinical manifestations, suggesting the existence of ME/ Verrucomicrobiota. 12,14,19
CFS subgroups, according to gastrointestinal disorders Diverse intestinal compartments are characterized by
linked to microbial gut dysbiosis and metabolic a specific spatial distribution of the microorganisms. 20-22
pathways. In fact, comorbid conditions such as irritable The human gut microbiota composition differs both
7-9
bowel syndrome (IBS) are often observed in patients with functionally and taxonomically based on aspects
ME/CFS, thereby indicating a potential involvement of such as age, antibiotic intake, and diet, 23-25 and the
the gut microbiota in the progression of the disease. In predominant genera within the human gut microbiota
8
particular, the involvement of the gut microbiota through are Bacillus, Blautia, Clostridium, Dorea, Enterococcus,
gut dysbiosis, the gut-brain axis, gut permeability, and Eubacterium, Faecalibacterium, Lactobacillus, Roseburia,
bacterial translocation in ME/CFS has been repeatedly and Ruminococcus (phylum Bacillota); Bacteroides
suggested. 5,6,8 It is widely understood that perturbation and Prevotella (phylum Bacteroidota); Bifidobacterium
of the gut microbiota (dysbiosis) and its metabolome (phylum Actinomycetota); and Escherichia (phylum
can affect several host processes, such as metabolism, Pseudomonadota). 12,14,26
inflammation, immunity, and brain function, and also The gut microbiota exerts beneficial effects for the
contributes significantly to the development of multiple human host, including metabolic and immunological
diseases related to the aforementioned host processes. 6,10 functions. 12,27 Intestinal microorganisms constitute
As ME/CFS prevalence continues to grow globally, essential regulators of the digestion process through the
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establishing the link between the gut microbiota and ME/ absorption of nutrients, and also through the synthesis
CFS is a pivotal aspect for delving into the disease’s etiology of diverse metabolites, such as amino acids, lipids, short-
and pathophysiology. Therefore, in the present review, we chain (2-6 C) fatty acids (SCFAs), and vitamins. 28,29
explore the potential links between the gut microbiota and Furthermore, the gut microbiota exerts a pivotal
ME/CFS. First, we review the evidence for bacterial and function in the maintenance of the intestinal epithelium
metabolomic dysbiosis in ME/CFS patients. Second, we integrity. Moreover, the gut microbiota generates a
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identify potential biomarkers particular to patient cohorts broad diversity of secreted biologically active compounds
across metabolic, microbial, and phenotypic domains. from undigested foods, such as histamine, polyamines,
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SCFAs, and tryptophan catabolites. 31,32 The metabolic
2. Human gut microbiota and microbial products of tryptophan (5-hydroxytryptamine, indole, and
metabolites kynurenine) have been identified as inhibitory compounds
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The human gut tract is composed of a broad microbial of neuroinflammation. SCFAs, such as acetate, butyrate,
community, with a density of around 10 – 100 trillion and propionate, constitute signaling molecules that locally
of microbial cells. The gut microbiota encompasses the modulate the gut function via enteroendocrine cells,
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microbial community in the gastrointestinal tract and influencing the metabolism of the brain, liver, and muscle,
34,35
consists of several microbial taxa, including bacteria, as well as the host energetic homeostasis. In addition,
archaea, viruses, protozoa, and fungal species, being SCFAs exert neuroactive effects via the induction of
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the most prevalent the bacteria domain, which form a neuroinflammatory responses.
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symbiotic relationship with the human gut. Archaeal The state related to the loss of gut homeostasis due to
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genera are present at reduced levels in the healthy human endogenous and exogenous factors is known as dysbiosis,
gut microbiota, with Methanobrevibacter smithii being the which triggers chronic inflammation and changes in
most abundant species. The eukaryotic microorganisms the release of microbial metabolites, including mucin,
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most frequently detected in the gut tract are fungi, such secondary bile acids, and SCFAs, which are pivotal for the
as the genera Candida and Saccharomyces. Protozoa regulation of both the immune and physiological functions
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such as Blastocystis have been identified in the human of the host. The gut microbiome homeostasis is essential
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gut microbiota and their presence has been often linked for preserving brain health, such as cognitive function and
Volume 2 Issue 1 (2025) 18 doi: 10.36922/mi.4783