Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)

Giuseppe Francesco Damiano Lupo,Edoardo Puglisi,Gabriele Rocchetti,Elena Manara,Matteo Bertelli,Lorenzo Lorusso,Luigi Lucini,Enrica Capelli

doi:10.1038/s41598-021-86425-6

Giuseppe Francesco Damiano Lupo, Edoardo Puglisi + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-86425-6

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Abstract

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe multisystemic disease characterized by immunological abnormalities and dysfunction of energy metabolism. Recent evidences suggest strong correlations between dysbiosis and pathological condition. The present research explored the composition of the intestinal and oral microbiota in CFS/ME patients as compared to healthy controls. The fecal metabolomic profile of a subgroup of CFS/ME patients was also compared with the one of healthy controls. The fecal and salivary bacterial composition in CFS/ME patients was investigated by Illumina sequencing of 16S rRNA gene amplicons. The metabolomic analysis was performed by an UHPLC-MS. The fecal microbiota of CFS/ME patients showed a reduction of Lachnospiraceae, particularly Anaerostipes, and an increased abundance of genera Bacteroides and Phascolarctobacterium compared to the non-CFS/ME groups. The oral microbiota of CFS/ME patients showed an increase of Rothia dentocariosa. The fecal metabolomic profile of CFS/ME patients revealed high levels of glutamic acid and argininosuccinic acid, together with a decrease of alpha-tocopherol. Our results reveal microbial signatures of dysbiosis in the intestinal microbiota of CFS/ME patients. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.

Highlights

Chronic Fatigue Syndrome (CFS), known as Myalgic Encephalomyelitis (ME), is a severe debilitating multisystemic disease that involves nervous1, immune2,3, endocrine4, digestive[5], and skeletal[6] systems and is associated with dysfunctions of both energy metabolism and cellular ion transport[7]
A reduction of Firmicutes and a significant increase in Bacteroidetes (p = 0.0005) were observed in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients compared to external controls (Supplementary Fig. 2), with a reduction of F/B ratio of about 60% in CFS/ME patients and of 50% in their relatives compared to the external control group
The present study reports alterations in the composition of both the fecal and salivary microbiota of CFS/ME patients, with more marked differences observed in the gut

Summary

Introduction

Chronic Fatigue Syndrome (CFS), known as Myalgic Encephalomyelitis (ME), is a severe debilitating multisystemic disease that involves nervous1, immune2,3, endocrine4, digestive[5], and skeletal[6] systems and is associated with dysfunctions of both energy metabolism and cellular ion transport[7]. Alterations of cell-mediated immunity, with a reduction in Natural Killer cells response and a strong increase in pro-inflammatory cytokines levels have been described in CFS/ME10,11. Microbiota of CFS/ME patients a higher relative abundance of genera Leptotrichia, Prevotella and Fusobacterium, and a decreased abundance of genera Haemophilus, Veillonella and Porphyromonas. These outcomes obtained by different studies probably reflect differences attributable to genetic backgrounds and to recruiting criteria of, which affect the homogeneity of sample populations. In light of the above considerations, in this study we applied a 16S rRNA high-throughput sequencing approach to analyze the oral and intestinal bacterial composition of ME/CFS in a population of Italian patients. A metabolomics pilot study on a small number of subjects representative for each population considered was conducted to evaluate the metabolic profile in feces

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