POS0466 RESISTANT STARCH DIET IMPROVES DISTINCT GUT MICROBIOTA STRUCTURES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ANTIPHOSPHOLIPID SYNDROME

Abstract

BackgroundFiber-poor diets are linked to a reduction in gut microbiota diversity and gut barrier integrity, which is thought to promote the susceptibility to chronic inflammatory disorders1,2. We have previously shown that dietary resistant starch (RS) improves lupus-like disease in a murine model of SLE3 through the modulation of microbiota composition. If similar dysbiotic microbial community structures exist in subsets of SLE patients and if a RS intervention may be efficacious in those patients remains unclear.ObjectivesTo test if the dietary RS content in SLE and SLE-related antiphospholipid syndrome (APS) affect gut microbial taxa associated with SLE in published cohorts to date.MethodsWe obtained stool and blood samples as well as diet history for up to 3 visits (0, 4 and 8 weeks) from 12 SLE (n=28) and 15 APS (n=44) patients as well as 20 controls (n=48) as previously published4-6. Microbiota composition was defined by 16S rRNA V4 region sequencing on the Illumina platform and correlated with dietary fiber content extracted from a diet questionnaire. We used the FDA reference list to determine dietary RS contents in patients` regular diets and defined RS quantities as being low if less than 2.5 g/day and as medium if 2.5 to 15 g/day. None of the patients achieved high RS greater than 15 g/day. Mann-Whitney or Kruskal-Wallis tests were performed to compare bacteria relative abundances among the different groups. Simple linear regression was performed to relate the bacterial abundance to RS content and other metadata.ResultsMedium intake of RS was associated with beneficial Bifidobacterium spp. in SLE patients (p=0.016) but not APS (p=0.509). Instead, APS patients who consumed medium quantities of RS in their diets had less gut bacterial taxa that are capable of producing cardiolipins (among them Collinsella; p=0.009) and Ruminococcus gnavus (p=0.0142), a species previously associated with lupus nephritis7. A recent Japanese metagenome-wide study8 associated Streptococcus spp. and related redox reaction genes with SLE, which may also affect oxidative processes in APS9. We therefore also explored Streptococcus levels in SLE and APS patients and found unexpectedly a significant reduction of streptococci in a subset of APS (p=0.004) but not SLE patients (p=0.451) in medium compared to low RS dietary content. Streptococcus abundance was correlated with both Collinsella (R2=0.3141; p=<0,0001) and Ruminococcus gnavus (R2=0.1687; p=<0,0056) in APS patients.ConclusionMedium compared to low RS quantities in the regular diets of SLE and APS patients were associated with unique alterations in gut microbial community structures. Bifidobacterium increased in SLE patients with diets containing medium RS whereas APS patients with medium RS carried less cardiolipin-synthesizing taxa and lupus-related pathobionts. In particular, Streptococcus species recently strongly associated with SLE and redox reactions in Japanese patients in a metagenome-wide study8, were significantly suppressed in APS patients on medium RS diets. This modulatory effect was not seen in SLE patients or control subjects consuming medium RS. Together, these findings support distinct dietary effects on autoimmune gut microbiomes depending on the disease state. They also suggest potential beneficial effects of increased RS content on gut microbiota in SLE and APS patients. Fully resolving gut microbial signatures and clinical characteristics in these patients may identify the ideal subset to benefit from an interventional pilot trial with RS.