Background Diets deficient in fibers are prevalent in modern societies and implicated in gut microbial dysbiosis contributing to the pathogenesis of chronic inflammatory disorders.1 A particular type of dietary fiber, resistant starch (RS) type 2, was shown to ameliorate disease in murine models of systemic lupus erythematosus (SLE).2 This effect was mediated by improvement of the gut barrier and growth inhibition of a translocating Lactobacillus strain. This Lactobacillus sp. was shown to drive lupus-related pathology in mice via the type I interferon pathway, and its genus was also enriched in a subset of SLE patients. Whether diet enriched in RS have similar effects in patients is unknown. We aimed to understand how dietary RS content influences gut microbial community structures in SLE and SLE-related antiphospholipid syndrome (APS) patients with well-defined microbiomes.3,4
Methods Stools and dietary information were collected from 12 SLE (n=28), 15 APS (n=44) patients and 20 control subjects (n=48) for up to 3 visits (0, 4 and 8 weeks) as previously described (3,4). Microbiota composition was defined by 16S rRNA V4 region sequencing. The FDA reference list was used to calculate the RS content. Patients’ diets were classified as low RS content if less than 2.5 g per day, medium RS if 2.5 to 15 g, and high RS above 15 g.
Results Lactobacillus spp. were significantly enriched in SLE patients (p=0.002) compared to non-disease controls. APS patients showed a similar trend (p=0.06), but SLE patients displayed higher relative abundance compared to APS (p=0.011). No significant association was observed between low-to-medium RS content and Lactobacillus. High RS content was not achieved in routine diets of SLE and APS patients in these cohorts. However, medium RS was associated with an outgrowth of Bifidobacterium in SLE patients (p=0.016). Also, medium RS correlated in APS patients with a reduction of cardiolipin-synthesizing bacteria from the Coriobacteriaceae family (p=0.011) including Collinsella (p=0.009) and Slackia genera (p=0.033), previously linked to APS.5,6
Conclusions The content of RS in patients` regular diets has a distinct impact on the gut microbiota composition depending on the autoimmune disorder. Medium levels of dietary RS were associated in SLE with increased Bifidobacterium, short-chain fatty acid producing bacteria known to promote immune homeostasis, and with decreased cardiolipin-producing commensals in APS. It remains to be tested in an interventional trial if high RS content corrects the outgrowth of Lactobacillus in these patients, but moderate levels of RS may provide already beneficial effects on other taxa potentially involved in the pathogenesis of these disorders.
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Acknowledgments The work was supported by grants from the National Institutes of Health (NIH) (R01AI118855, T32AI07019), Arthritis National Research Foundation, Arthritis Foundation, Lupus Research Alliance, and Maren Foundation.
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