Oral Microbiota Profile in a Group of Anti-AChR Antibody–Positive Myasthenia Gravis Patients

Abstract

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies directed against the postsynaptic membrane at the neuromuscular junction. Perturbation of gut microbiota is thought to contribute to the development of MG, as reflected by fecal metabolomic signatures in humans, but there have been few studies on the relationship between oral microbiota profile and MG. The current study evaluated the correlation between oral microbiota composition and diversity and anti-acetylcholinereceptor (AChR) antibody–positive MG by comparing oral microbiota communities of patients (n = 20) and healthy controls (HCs; n = 20) by 16S rRNA gene sequencing. Principal coordinate analysis and Adonis analysis revealed significant differences in oral microflora profile between the twogroups. Compared to HCs, the abundance of the phyla Firmicutes and Actinobacteria and genera Streptococcus, Rothia, and Lachnoanerobaculum was significantly increased whereas that of phyla Proteobacteria and Spirochaetotaand genera Neisseria, Haemophilus, and Treponema was significantly decreased in MG patients. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the biosynthesis of ansamycins and amino acid metabolism pathways were altered in MG. These results indicate that oral microbiota composition is perturbed in patients with anti-AChR antibody–positive MG, providing new potential avenues for targeted therapeutic interventions.

Mendelian randomization study revealed a gut microbiota-neuromuscular junction axis in myasthenia gravis

“…Though phylum Actinobacteria represents only a small percentage in the four major phyla of the gut microbiota, accumulating evidence has suggested their beneficial effects in many pathological conditions. Actinobacteria was found to be significantly decreased in the fecal sample of MG patients compared with controls in several cross-sectional studies 12,26,27 ; while the inconsistent result showing increased abundance of Actinobacteria in the saliva of MG patients 28 is expected to be attributed to the difference in distribution of intestinal and oral flora. Rinaldi et al investigated the clinical efficacy of the therapeutic administration of vital bifidobacteria in MG and suggested that this probiotic therapy improved the symptoms of the experimental autoimmune MG model and decreased serum anti-rat AChR antibody levels 29 .…”

The Role of Human Microbiota in Myasthenia Gravis: A Narrative Review

“…The conflicting results between oral and gut microbiota deserve further investigation. However, since the gastrointestinal tract is widely populated by different bacterial species coming from the oral cavity, microbiota analyses must consider the large variety of the gastrointestinal bacterial flora in the various tracts [ 65 ]. A final consideration should be reserved for the comparison of gut microbiota alterations between MG and other autoimmune diseases.…”

“…In particular, the abundance of the phyla Firmicutes and Actinobacteria was increased in patients with MG, while Proteobacteria were the predominant phylum in healthy controls. Furthermore, they evidenced that bacteria of the genera Streptococcus , Rothia , Lachnoanaerobaculum and Oribacterium were increased in MG patients while the proportions of Neisseria , Haemophilus and Treponema were significantly decreased when compared with healthy controls [ 65 ]. Oral abundance of Firmicutes was, in contrast with their reduction in the gut microbiota, reported in other studies.…”

“…There are several pathogenetic mechanisms through which oral dysbiosis may affect the MG onset or disease course: (1) Streptococcus may modulate peroxisome proliferator-activated receptor γ affecting the balance between Tregs and Th17 [ 66 , 67 ]; (2) Rothia antigens can activate lymphocytes as well as induce macrophage activation and TNF-α production which can directly destroy AChRs or it may induce the differentiation and the growth of B cells allowing AChR antibody production [ 68 , 69 ]; (3) oral dysbiosis may alter the biosynthesis of ansamycin and some amino acids (e.g., valine, leucine, isoleucine, glutamine). Huang et al hypothesized that the increased ansamycin, which is a macrolide, may interfere with neuromuscular transmission, unmasking MG symptoms according to the well-known effects of macrolides on the NMJ [ 65 , 70 ]. On the other hand, because some metabolites have immunomodulating properties, the altered amino acid metabolism may play a further role in the MG pathogenesis.…”

Machine learning strategy for identifying altered gut microbiomes for diagnostic screening in myasthenia gravis

“…Another analysis revealed that MG is associated with a lower abundance of Verrucomicrobiaceae and Bifidobacteriaceae and an increased abundance of Bacteroidetes and Desulfovibrionaceae ( Moris et al, 2018 ). Specially, Huang et al found that AChR positive MG patients also experience changes in their oral microbiota ( Huang et al, 2022 ). Our study identified bacterial genera for which the abundance differed in individuals with and without MG and applied two microbiomes-based ML models to identify key bacterial taxa.…”