Abstract
PurposeFatty acid (FA) abnormalities are found in various inflammatory disorders and have been related to disturbed gut microbiota. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with altered gut microbial composition. We hypothesized that there is an altered FA profile in CVID patients, related to gut microbial dysbiosis.MethodsPlasma FAs were measured in 39 CVID patients and 30 healthy controls. Gut microbial profile, a food frequency questionnaire, and the effect of the oral antibiotic rifaximin were investigated in CVID patients.ResultsThe n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) (1.4 [1.0–1.8] vs. 1.9 [1.2–2.5], median (IQR), P < 0.05), and docosahexaenoic acid (DHA) (3.2 [2.4–3.9] vs. 3.5 [2.9–4.3], P < 0.05), all values expressed as weight percent of total plasma FAs, were reduced in CVID compared to controls. Also, n-6 PUFAs (34.3 ± 3.4 vs. 37.1 ± 2.8, mean ± SD, P < 0.001) and linoleic acid (LA) (24.5 ± 3.3 vs. 28.1 ± 2.7, P < 0.0001) and the FA anti-inflammatory index (98.9 [82.1–119.4] vs. 117.0 [88.7–153.1], median (IQR), P < 0.05) were reduced in CVID. The microbial alpha diversity was positively associated with plasma n-6 PUFAs (r = 0.41, P < 0.001) and LA (r = 0.51, P < 0.001), but not n-3 PUFAs (P = 0.78). Moreover, a 2-week course of rifaximin significantly reduced the proportion of n-6 PUFAs (P = 0.04, UNIANOVA). Serum immunoglobulin G (IgG) levels correlated with plasma n-3 PUFAs (rho = 0.36, P = 0.03) and DHA (rho = 0.41, P = 0.009).ConclusionWe found a potentially unfavorable FA profile in CVID, related to low IgG levels. High plasma n-6 PUFAs were related to increased gut microbial diversity and altered by rifaximin therapy.
Highlights
Sixteen patients completed all three measurements, and we found no significant changes in plasma wt% of n-3 polyunsaturated FAs (PUFAs) (P = 0.27), n-6 PUFAs (P = 0.67), or Monosaturated FAs (MUFAs) (P = 0.53) during these measurements (Supplemental Fig. S1), suggesting that intra-individual Fatty acid (FA) profiles are relatively stable in Common variable immunodeficiency (CVID) patients
When categorizing CVID patients according to presence or absence of specific clinical complications, such as enteropathy, splenomegaly, lymphoid hyperplasia, granulomas, organ-specific autoimmunity, autoimmune cytopenia, or bronchiectasis, we found no differences in the proportions of plasma n-3 PUFAs, n-6 PUFAs, and MUFAs between groups (Supplemental Table S4)
Our main findings in this pilot study were as follows: (i) CVID patients have a potential unfavorable FA profile with reduced plasma FA proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and a reduced anti-inflammatory index; (ii) n-6 PUFAs and linoleic acid (LA) were decreased in CVID patients and were positively associated with gut microbial alpha diversity; (iii) a 2-week course of oral rifaximin known to reduce gut microbial diversity led to a reduction of n-6 PUFAs; (iv) serum immunoglobulin G (IgG) levels were positively associated with plasma n-3 PUFAs, DHA, and omega 3 index; (v) the altered plasma FA proportions of n-3 and n-6 PUFAs did not seem to be related to altered dietary intake, intestinal absorption, or the presence of CVID enteropathy
Summary
A large proportion of the patients (70–80%) have non-infectious autoimmune and/or inflammatory complications, such as splenomegaly, lymphadenopathy, enteropathy, granulomas and lymphoid interstitial pneumonitis [3, 4] The etiology of these inflammatory and autoimmune complications is largely unknown, but we have previously shown an association with altered gut microbial composition and blood lipids [5, 6]. Fatty acids (FAs), both free and as part of complex lipids, play a number of key roles in metabolism and cellular functions They constitute a major component of cell membranes, act as precursors of extracellular signaling molecules, and influence membrane-derived intracellular signaling pathways. These factors are important for human health and disease risk, and numerous studies support a role for FAs in various autoimmune and inflammatory disorders [7, 8]. The n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to have anti-inflammatory properties, whereas the n-6 PUFA arachidonic acid (ARA) appears to mediate inflammatory reactions, at least partly by acting as precursors for various bioactive lipid mediators with opposing biological effects
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