In the present study, including 140 patients, 22% had a positive ASCA IgG test result. This frequency of ASCA positivity in subjects with morbid obesity was at least of the same order of magnitude as the previous publication by Salamati et al. [1]. Our study did however not show an association between ASCA and BMI. This might have been due to the fact that our study included subjects with morbid obesity only, limiting interpretations of results to this BMI range. On the other hand, an association was detected between ASCA IgG-positivity and body fat mass, suggesting that in a population of subjects with morbid obesity, total amount of body fat is a better predictor of ASCA than the relative amount of body fat.
The findings of a relationship between ASCA and adiposity in humans are interesting considering the use of Saccharomyces cerevisiae as a growth promoter in the animal husbandry [1, 2]. Consumption of the main dietary sources of baker’s/brewer’s yeast was however not reflected by the plasma levels of ASCA IgG in our study, indicating that ASCA IgG formation was unrelated to yeast intake. Additionally, we did not find any association between the total intake of these yeast-containing foods and the anthropometrical indices BMI, body fat mass or body fat percentage. This finding was independent of ASCA status, suggesting that effect modification was unlikely. In all, these results do not support a causal relationship between the consumption of baker’s/brewer’s yeast and obesity in humans.
The amount and type of yeast in the gut may also depend on the nutrient availability within the gut. A study which reported associations between nutrients and the presence of fungal populations in fecal samples did however not find any relationship between Saccharomyces and the nutrient composition of the diet, either recent or long term diet [18]. In the present study, there were no associations between ASCA IgG and either energy yielding nutrients or total energy intake.
In addition to the association between ASCA IgG and body fat mass, our study showed an association between ASCA IgG positivity and serum CRP. Obesity is associated with a state of low-grade inflammation, including increments in serum CRP [19]. There is also some evidence suggesting a positive association between obesity and immunoglobulin levels [20,21,22], including a study which reported concomitant elevations of anti-food IgG and CRP in obese compared to normal weight juveniles [22]. This relates to our finding that ASCA IgG-positivity, CRP and body fat mass were all inter-correlated. Together with a study which showed that IgG directed against specific enteric bacterial antigens may be related to obesity and the associated metabolic inflammation [6], these results indicate that certain dietary or other luminal (microbial) antigens may be linked to the generalized inflammation commonly seen with increased adiposity. In contrast to our finding, Salamati et al. [1] did not demonstrate a correlation between serum CRP and ASCA values. The higher sample size in our study and some differences in inclusion criteria may have accounted for this difference. A limitation is that neither we, nor the study by Salamati et al. [1], measured other inflammation markers in addition to CRP. Adipose tissue has many endocrine functions and a large range of signaling molecules may be released either from the adipose tissue and/or immune cells within the adipose tissue, implying that other inflammation markers could be the ones that are mechanistically linked to ASCA IgG.
Evidence suggests an association between increased gut permeability and systemic inflammation in obesity, and the association may be bi-directional [5]. Moreover, high concentrations of ASCA have been found in Crohn’s disease [23, 24] and other diseases associated with increased gut permeability, such as celiac disease and type 1 diabetes mellitus [25,26,27]. A “leaky gut”, with increased translocation of Saccharomyces cerevisiae (or related antigens) could thus be one potential explanation for the increased ASCA IgG concentrations and their association with CRP. In the present study we measured zonulin, a marker of tight junction permeability in the gut [26]. We found that elevated zonulin levels were more frequent in subjects with ASCA IgG-positivity than in subjects negative for ASCA IgG and the elevated levels correlated significantly with increasing concentrations of CRP. However, the observed difference in zonulin between the ASCA IgG-positive and the ASCA IgG-negative group did not reach statistical significance. A study of patients with Crohn’s disease also showed a non-significant trend between elevated ASCA IgG and intestinal permeability, but similar to our study, could not demonstrate a clear cut association [23]. Thus it appears that the elevated ASCA concentrations cannot be explained solely by an increased antigenic challenge due to a leaky gut. Genetic pre-disposition, deviations in the gut microbiota and cross-reactivity of ASCA with other antigens could be other causes for the raised ASCA IgG concentrations and their association with body fat mass and/or inflammation in a sub-group of obese subjects. These aspects were not explored in the present study, but could be directions for future research.
Strenghts and limitations
Strength of the study is that it was based on a well characterized population with the assessment of a wide range of demographic, clinical and biochemical data, thereby reducing the risk of unknown confounders. A limitation is that the many variables that have been addressed also increased the risk of a type I statistical error. Information about the use of medications was however incomplete. Thus, we cannot rule out that the use of certain drugs could have influenced our findings. Information regarding certain autoimmune conditions was also lacking. In the present study, the 95% CI for the proportion of IgG positive samples ranged between 16% and 30%, which is comparable to the frequency of IgG positivity found in diseases of autoimmune origin, such as type 1 diabetes mellitus [27], systemic lupus erythematosus [28] and microscopic colitis [29], but lower than in Crohn’s disease [30]. No significant association was however detected between ASCA and disorders such as hypothyroidism or diabetes (the majority of the diabetic patients had type II diabetes). Moreover, patients with organic gastrointestinal disorders or former major gastrointestinal surgery were excluded from the study.
The lack of a normal weight control group represents a limitation with respect to reference values for ASCA, but based on the aforementioned studies [27,28,29,30], the frequency of IgG positivity in our study was higher than what would be expected in healthy control subjects, in whom the reported prevalence ranged between 0 and 5.0% [27,28,29,30]. This is also in accordance with the previous publication of ASCA and obesity by Salamati et al., in which none of the normal weight controls were ASCA positive [1].
Other methodological considerations of the present study include the dietary assessment tool and our definition of yeast intake: Firstly, calculation of the exact intake of this yeast was not possible based on our FFQ. We therefore chose to focus on two major dietary sources of Saccharomyces cerevisiae, namely bread, buns and other baked goods (baker’s yeast) and beer (brewer’s yeast). Results from our study did however not reveal any significant associations between ASCA and other food groups or between ASCA and total alcohol consumption. Secondly, because the FFQ that we applied was designed to study the habitual diet during the last year, conclusions cannot be made regarding the impact of more recent diet or diet early in life. Also, recalling food intake over a year may be inaccurate, but with respect to the main dietary sources of yeast, we believe that significant fluctuations in intake during the year were unlikely. This is because bread is regarded a staple food in Norway that is regularly consumed all year round. Beer on the other hand probably contributes less to the total intake of yeast as compared to bread.