Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial

Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies with resultant multiple organ damages. The great heterogeneity of clinical manifestations along with intricate underlying pathogenesis impedes the development of lupus treatment. With the belimumab as a beginning, a surging number of clinical trials testing various targeted agents (B cell markers, costimulatory molecules, cytokines and chemokines, cytosolic and endosomal nucleic acid sensors, intracellular kinases and others) have been carried out in the last decade. However, no specific medicine has been identified with definite and general effects including the approved belimumab and anifrolumab. Till now, the glucocorticoids and unselective immunosuppressors have been serving as the primary treatments, under which circumstances, we need to seek alternative therapies through multiple pathways.

Trillions of microbes including bacteria, fungi and viruses reside in the human guts and interact with each other as well as with the host by multiple mechanisms, by which they can build and regulate the host immune system [1]. SLE which is featured by dysregulated immunity and the production of antibodies targeting self-antigens can not only be born genetically but also can be triggered by environmental factors such as toxic chemicals and infections. It has been revealed that the gut microbe plays a role in the development of multiple immune-mediated disorders including inflammatory bowel disease (IBD) [2,3], type I diabetes [4,5], allergic diseases [6], and other autoimmune diseases [7,8]. Although the crosstalk between gut dysbiosis and immune disorder is so intricated that the causal relationship between them is controversial, a batch of research indicated that interventions of the gut microbiome towards the healthy type can alleviate the symptoms of SLE, which showed the veritable connection between the gut microbiome and the development of SLE.

Fecal microbiota transplantation (FMT) was initially proven effective in patients with recurrent or refractory Clostridium difficile infection (CDI) [9,10]. Since then, increasing clinical trials focused on the efficacy of FMT in variable diseases, from IBD to metabolic diseases, and even cancers [[11], [12], [13]]. The studies showed varied efficacies of FMT in disease treatments, while it did benefit some patients, implying the potential of FMT as a novel choice for the diseases for which the current therapies are limited, although the underlying mechanisms are not well understood.

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