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Lignans redress autoimmunity and achieve curative effects on myasthenia gravis by ameliorating the gut microbiome

ABSTRACT:

Myasthenia gravis (MG) is a serious inflammatory autoimmune disease characterized by continuous production of autoantibodies against targets in the neuromuscular junctions, resulting in muscle weakness. Autoimmunity has long been presumed to be irreversible. The current therapeutic regimens may alleviate the disease conditions, but curative outcomes can hardly be achieved. In this study, we assessed the curative potential of lignans on MG. Lignans, prevalent in edible plants such as flaxseed (flaxseed lignans, FL), have been shown to possess the intrinsic ability to inhibit inflammation. However, whether lignans may reverse the autoimmune state and provide curative therapies for MG is unknown.We established a C57BL/6J mouse model of experimental autoimmune myasthenia gravis (EAMG), using R97-116 peptide as the antigen, to evaluate the effects of FL on MG and investigate the molecular mechanisms of effects by multi-omics analyses. FL treatment effectively halted the progression of EAMG as reflected by the markedly alleviated muscle atrophy and significantly elevated muscle strength. The gut microbiome composition was profoundly remodeled, the gut barrier was significantly ameliorated, and the levels of the anti-R97-116 IgG autoantibody were radically lowered, all signs suggesting reversed conditions of the experimental MG by lignans. Mechanistically, the curative effects were associated with the inhibition of the Rap1gds1/Cdc42 signaling pathway. Lignans could reverse MG pathogenesis and achieve curative effects on MG by redressing the inflammatory autoimmune state through ameliorating the gut microbiome, modulating the metabolites, mitigating the gut barrier damage, and inhibiting the Rap1gds1/Cdc42 signaling pathway.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12842 | MetaboLights | 2025-10-24

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12842_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12842_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12842_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12842_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Background The gut microbiota plays a significant role in modulating the growth and function of host muscle, and microbiota transplantation experiments provide compelling evidence of its capacity to improve muscle quality. Feeding faba beans improves the muscle quality of Yellow River carp. However, the changes in gut microbiota, along with the specific microorganisms, metabolic pathways, and regulatory mechanisms linked to the enhancement of muscle quality following faba bean consumption remain to be elucidated.Results After a 6-week feeding trial with faba beans, growth performance decreased, but muscle texture improved (P < 0.05). Gut microbiota structure also changed, with increased relative abundances of Aeromonas, ZOR0006, Cetobacterium, and Atopobium. Following 8 weeks of whole-intestinal microbiota transplantation (WIMT) from faba bean-fed donors to basal diet-fed recipients of Yellow River carp, growth performance remained unchanged (P > 0.05), while muscle texture improved (P < 0.05). This improvement was mainly due to increased small-diameter muscle fibers, higher collagen levels, and reduced muscle fat content (P < 0.05), which partially replicated the muscle texture of donor fish. Moreover, WIMT promotes intestinal structure and barrier integrity, with significant changes in gut microbiota structure and metabolic profile. WIMT improved the muscle quality of Yellow River carp by regulating mitochondrial autophagy and adipocytokine signaling pathways through the gut-muscle axis. Cetobacterium somerae (C. somerae) and its metabolites, such as acetic acid, played a crucial role in this process. Further feeding experiments demonstrated that C. somerae and acetic acid reduced the crude fat content of muscle while increasing the crude protein and collagen (P < 0.05). C. somerae also mitigated muscle protein degradation under inflammatory and enhanced collagen (P < 0.05), thereby improving muscle texture.Conclusion This study establishes that gut microbiota enhance muscle quality in Yellow River carp through WIMT, identifies C. somerae and its metabolite acetic acid as key contributors. The findings provide novel evidence for fish gut-muscle axis research and offer new scientific basis for improving Yellow River carp muscle quality.

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Lignans redress autoimmunity and achieve curative effects on myasthenia gravis by ameliorating the gut microbiome

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