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Microbes & Immunity Microbial involvement in ME/CFS

synaptic plasticity, thereby inhibiting neuroinflammation rise to a disrupted gut barrier (“leaky gut”), bacterial
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processes and safeguarding from neurodegenerative translocation, subsequent systemic chronic inflammation,
diseases by maintaining microglial cells in a healthy mature along with neuroinflammation and neuroimmune
condition. 33 impairment that may impact the brain and lead to ME/
CFS. While the precise mechanism underlying this
6
3. Gut microbiota dysbiosis and ME/CFS phenomenon remains unclear, one proposed explanation is
Alterations in the gut microbiome have been linked to that the rise in Enterobacteriaceae associated with dysbiosis
diminished microbial diversity, a reduction of commensal might drive intestinal inflammation and increased
gut microbiota, and an increase in proinflammatory permeability, potentially due to elevated concentrations
molecules leading to a dysregulated host immune response of lipopolysaccharide (LPS) produced by these bacteria,
or adjustment of the gut in individuals with ME/CFS. In causing metabolic endotoxemia, which has been reported
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48
addition, several recent studies have reported comorbidity in ME/CFS. The inquiry into whether a leaky gut also plays
40
with gastrointestinal disorders, such as IBS. 8 a role in ME/CFS has been addressed by Shukla et al., who
found greater bacterial translocation and heightened levels
Diverse studies have shown gut dysbiosis in ME/CFS of IgA and IgM to LPS in patients with ME/CFS than in
(Table 1), although the results vary depending on the healthy controls. Considering that bacterial translocation
characteristics of the trials. Wang et al. , in a retrospective can induce systemic inflammation, disrupt blood-
10
review, reported that the proportions of gut microbial brain barrier, and lead to neuroinflammation, diverse
phyla between patients with ME/CFS and healthy controls researchers speculate that this process may account for the
are distributed as Bacillota (67.1% vs. 78.9%), Bacteroidota development of neurological anomalies in ME/CFS. 49,50
(21.2% vs. 10.8%), Actinomycetota (1.8% vs. 2.6%), and Figure 1 shows the hypothetical pathways regarding the
other phyla (10.2% vs. 8.9%); therefore, a decrease of the relationship between gut microbiome and ME/CFS.
Bacillota/Bacteroidota may be associated with ME/CFS.
In addition, the microbial a-diversity (i.e., the observed Other studies reported increased oxidative stress
51
number in taxa or the relative abundances in those taxa in ME/CFS. Increased oxidative stress and decreased
of an average sample within a habitat type) of the gut resting antioxidant levels during periods of rest have been
microbiome was reduced and there was a significant noted in patients with ME/CFS when compared to healthy
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disparity within the general configuration of the gut controls. Furthermore, heightened urinary 8-hydroxy-
microbiome b-diversity (i.e., the variability in community deoxoguanosine (8-OHdG) levels, an indicator of oxidative
composition or the identity in taxa observed among DNA degradation, have been associated with symptoms of
samples within a habitat) in individuals with ME/CFS malaise and depression in individuals with ME/CFS. In
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compared to the non-affected controls. Thus, the role of addition to dysbiosis and metabolic endotoxemia, other
the gut microbiota in the pathogenesis of ME/CFS is not factors may be also involved in an oxidant/antioxidant
yet clarified. imbalance, such as viral infection, stress, depression, and
reduced antioxidants. 54,55
Several studies showed differing results regarding the
abundance of the bacterial phyla in the gut microbiome. Gut microbiota also possesses the capacity to generate
Increased abundance was found in the phyla Bacteroidota neurotransmitters and influence their signaling pathways.
(genera Alistipes, Bacteroides, and Paraprevotella), 5,8,40,46 Dysbiosis can interfere with the synthesis and equilibrium
Bacillota (genera Blautia, Clostridium, Coprobacillus, of neurotransmitters, including gamma-aminobutyric
Enterocloster, Eggerthella, Erysipelatoclostridium, acid and serotonin, which are crucial for cognitive
Lachnoclostridium, Phascolarctobacterium, Ruminococcus, function, mood regulation, and other brain activities.
Ruminococcaceae_UCG_014, Ruthenibacterium, Sellimonas, Disruptions in neurotransmitter production and signaling
and Tyzzerella), 5,41,44-46 and in the phylum Pseudomonadota. processes might play a role in the neurological and
42
In contrast, a decrease of the abundance was reported in the psychological manifestations observed in subjects with
following phyla: Actinomycetota (genus Bifidobacterium), 40,42 ME/CFS. Abnormalities in the levels of tryptophan, a
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Bacteroidota (genera Bacteroides, Coprobacter, and neurotransmitter modulated by the microbiome, have been
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Phocaeicola), 8,41,45 and Bacillota (genera Anaerostipes, associated with ME/CFS. In addition, the gut microbiome
Eubacterium, Faecalibacterium, and Roseburia). 5,8,40,42,44,45,47 directly impacts vagal nerve stimulation, although this
relationship may be bidirectional, as the vagal nerve also
It has been suggested that gut dysbiosis can cause 6
immunometabolic disturbances (e.g., diminished innervates the colon.
generation of antimicrobial peptides and SCFAs, perturbed Finally, dysbiosis can modify the synthesis and
tryptophan/kynurenine pathway metabolism), giving accessibility of various metabolites such as SCFAs and

Volume 2 Issue 1 (2025) 19 doi: 10.36922/mi.4783