Kylie Benavides

Background: Systemic lupus erythematosus (SLE) is an autoimmune condition that results from dysregulation of the innate and adaptive immune systems¹. This disease is characterized by the presentation of autoantigens and the production of autoantibodies by B cells, as well as stimulation of autoreactive T cells¹. Additionally, the immune system is unable to clear the autoantigens that remain once host cells are killed, leading to further overactivation of the immune response and the potential for widespread organ damage¹. SLE involves multiple systems, including renal, neurological, and dermatological entities². Current therapies for SLE include agents such as glucocorticosteroids, which increase a patient’s risk of cataracts, osteoporosis, fractures, and coronary artery disease and generate 80% of the organ damage recorded in SLE patients³. Despite the proven causal effect of gut microbiome composition on SLE risk⁴ and the association of several bacterial species with lupus activity⁵, only one clinical trial exists that explores the use of fecal microbiota transplant (FMT) in SLE patients⁵. The mechanism of this treatment is not well understood in SLE but has been further researched in other autoimmune conditions⁶.

Objective: This narrative review explores the mechanism of FMT in ulcerative colitis and the effects of elevating the number of bacteria that produce short-chain fatty acids (SCFA) to determine FMT applicability to SLE patients.

Search Methods: An online search in the PubMed database was conducted for sources from 2020-2024 using the following keywords: “systemic lupus erythematosus”, “fecal microbiota transfer”, “ulcerative colitis”, “short-chain fatty acids”, and “Firmicutes”.

Results: Studies demonstrated that ulcerative colitis-induced mice had elevated levels of Helicobacter, Bacteroides, and Clostridium and reduced numbers of Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella, and Odoribacter, returning to levels that did not statistically differ from control mice after FMT ⁶. All species elevated by FMT produced SCFAs⁶, a fermentation by-product shown to protect SLE-induced mice from vascular dysfunction by preventing increases in blood pressure and organ hypertrophy⁷ through inhibition of histone deacetylases and activation of G protein-coupled receptor 43 (GPR43)⁷. A 12-week clinical trial administering 30 1g capsules of donor fecal microbiota once a week for 3 weeks to SLE patients increased numbers of SCFA-producing Firmicutes bacteria and created a 42% decrease in disease activity in these patients⁵. Additionally, Prevotella, Veillonella, and Burkholderiales bacterium, all of which are associated with systemic inflammation, were reduced after FMT treatment, further improving clinical outcomes⁵.

Conclusion: Studies in ulcerative colitis have revealed that FMT can decrease inflammation by elevating the number of SCFA-producing bacteria⁶. SCFAs have vascular-protective effects in SLE⁷, providing a potential mechanism for improved clinical outcomes in SLE patients who underwent the FMT clinical trial⁵. The use of FMT for SLE treatments has proven to be effective,⁵ but warrants further studies surrounding the optimal dose and long-term consequences of this therapy. Because FMT did not increase the risk of infections in these patients⁵, FMT may reduce the need for traditional immunocompromising therapies that put patients at serious risk of infection, organ damage, and future disease³.

Works Cited:

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