The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives

Abstract

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established. Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS. In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS. Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…Various viral infections can trigger low-grade inflammation, including: Post-Acute Infectious Syndromes (PAIS): This relatively new medical term refers to symptoms of long-term consequences of acute infections caused by numerous pathogenic agents, including viruses such as SARS-CoV-2 [ 144 ]. The main manifestations of PAIS encompass general poor functional status, exercise intolerance, debilitating fatigue, signs of depression, cognitive and sensory impairments, dysautonomia, musculoskeletal complaints, flu-like symptoms, as well as disturbances in gut microbiota and various immunologic dysfunctions [ 144 , 145 ]. Besides SARS-CoV-2, other viruses like Ebola, Dengue, Polio, SARS (SARS-CoV-1), Chikungunya, EBV, West Nile virus, and potentially alphaviruses, Ross River virus, and VZV have also been implicated in initiating PAIS [ 144 ].…”

From HHV-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID

“…Patients with inflammatory bowel disease often experience depression, which is indicated by various markers of leaky gut such as calprotectin and LBP [41]. There have been studies conducted on MDD and CFS that have found evidence of gut dysbiosis endotypes, which suggest an association with increased gut permeability and pro-inflammatory potential [42][43][44][45][46].…”

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery

“…Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that manifests in various physiological systems and is characterized by unresolved fatigue and post-exertional symptom exacerbation (PESE) [ 1 , 2 ]. The onset of ME/CFS is often connected to viral/bacterial infection [ 3 , 4 ], with the herpesviruses being most implicated [ 5 – 7 ]. However, there are no widely-established clinical biomarkers for the condition and much of the disease pathogenesis remains unknown.…”