Examining the role of fiber and its effects on the gut microbiome of diabetes-predisposed children
Lack of association between dietary soluble fiber intake and islet cell autoimmunity leads to questions about the role of diet-related gut microbiome alterations and their influence on immunomodulation.
Beyerlein A, Liu X, Uusitalo UM, et al. Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study. Am J Clin Nutr. 2015;102(2):345-352.
The objective of this study was to evaluate the TEDDY cohort for dietary soluble fiber intake and to evaluate the association between intake and presence of islet cell autoantibody production in young children.
Prospective cohort study
Of the 8,676 children enrolled in the TEDDY cohort study, the present study analyzed data from 3,358 subjects. Of those, 2,912 were from the United States and 446 were from Germany. Participants had an increased genetic risk of type 1 diabetes, defined as either the presence of a high-risk HLA gene or the presence of type 1 diabetes in a first degree relative. The children were enrolled into the TEDDY cohort at age 4 months or under, and they were monitored for soluble fiber intake for 48 months.
Study Parameters Assessed and Primary Outcome Measures
Researchers collected and analyzed 17,620 food records for children between the ages of 9 months and 48 months. Hazard ratios were calculated for the development of any islet cell autoantibody or multiple islet cell autoantibodies, as well as hazard ratios for the development of type 1 diabetes, stratified by soluble fiber intake. The primary outcome studied was the development of islet cell autoimmunity, which was assessed every 3 months. Islet cell autoimmunity was defined as the presence of a confirmed islet cell autoantibody on 2 or more consecutive visits. Type 1 diabetes diagnosis, as defined by the American Diabetes Association, was monitored as another primary outcome measure. Dietary records were collected by 24-hour dietary recall at 3 months of age. Dietary records were then collected by 3-day diet diary every 3 months until 12 months. After 12 months of age, dietary records were collected by 3-day diet diary every 6 months until 48 months old. The participants’ parents and guardians were advised to collect 2 weekdays and 1 weekend day. No dietary advice was provided.
Soluble fiber intake was explored both as a continuous (per gram) variable and also as a categorical (highest vs lowest quintile of intake; above vs below mean intake) variable. Cox regression models were used to assess the hazard ratios for development of subsequent islet cell autoimmunity and development of type 1 diabetes for intake of soluble fiber. The participants were evaluated for development of islet cell autoimmunity or type 1 diabetes until 5 years old based on their soluble fiber intake from 3 to 48 months of age. Short-term associations between primary outcomes and soluble fiber intake at 3 and 6 months were also evaluated.
Of the participants, 7.2% developed any islet autoantibody at a median age of 2.3 years old; 4.5% developed multiple islet cell autoantibodies at a median age of 2.7 years old; and 2.1% were diagnosed with type 1 diabetes at a median age of 3.6 years old. For 1,000 kcal of average food intake, the mean soluble fiber intake was 2.8 grams, and the mean total fiber intake was 8.9 grams. The lowest quintile of soluble fiber intake was under 1.8 grams, and the highest quintile was over 3.3 grams. No statistically significant associations were observed between the development of islet cell autoantibodies in the highest soluble fiber intake group compared to the lowest soluble fiber intake group. No statistically significant association was observed for development of islet cell autoimmunity for every gram increase of soluble fiber consumed. Significant associations were not found for soluble fiber intake levels in the first 12 months of life, nor in the first 2 years of life. No significant short-term associations were found for highest levels of soluble fiber intake and development of islet cell autoimmunity in the next 3 or 6 months.
The authors of the current study hypothesized that dietary soluble fiber would decrease the risk of developing type 1 diabetes–associated islet cell autoantibodies for a number of reasons. First, type 1 diabetes is on the rise in Western countries, and Western countries are known to be deficient in fiber.1,2 Secondly, research has acknowledged the role of soluble fiber in maintaining the gut microbiome. Dietary fiber enhances short chain fatty acid (SCFA) production by gut bacteria and may contribute to regulation of cytokine release at the genome level.3 Certain studies have also pointed to dietary fiber intake as a way to alter gut microbial composition in autoimmune disorders.4
Upon finding the lack of association in the current study between dietary soluble fiber intake and islet cell autoimmunity, the authors questioned the role of diet-related gut microbiome alterations and their influence on immunomodulation. The authors also questioned the role of SCFA production in immunomodulation.
A number of factors must be considered when interpreting the findings of the current study. First, the source of soluble fiber in the diet may warrant further investigation. Those children with the highest quintile of soluble fiber intake may have received it from whole grain intake. Nielsen, et al, in a 2014 review, explained that high intake of gluten-containing cereals is associated with an increased risk of islet cell autoimmunity in animal studies.5 Additionally, Nielsen explains that up to 10% of type 1 diabetic patients also have celiac disorders. He also explains that the gluten content of the diet can negatively impact the composition of gut microbiota, perhaps acting as a confounding variable to the current findings.
Additionally, these and other findings raise concerns about the consistency and predictability of dietary influences on the gut microbiota in both healthy populations and type 1 diabetics. Some studies have shown an altered gut microbiome in children with islet cell autoimmunity.6 One study evaluated stool samples from 22 children with islet cell autoantibodies and compared them to 22 health controls over 3 years. Children who had islet cell autoimmunity had reduced connectivity between bacterial networks and an increased amount of isolated nodes within the microbiome. This raised concerns about the flexibility, adaptability, and diversity of the gut microbiome in children with islet cell autoimmunity. Dietary fiber intake has not yet been shown to influence network connectivity in type 1 diabetics. Another study found that, in 16 type 1 diabetic children, there were significant differences in the number of Bifidobacteria, Lactobacillus, and Clostridium species, as compared to healthy controls.7 However, these alterations have not been consistently reproduced in other studies. Another study in children with islet cell autoimmunity showed altered Bacteroides numbers.8 Some studies have noted an increase in Bacteroides, while others show a decrease in Bacteroides in patients with type 1 diabetes.5 Butyrate-producing organisms have been found to be higher in controls when compared to type 1 diabetics. Certainly, the current research has determined very few, if any, definitive and consistent microbiome alterations in type 1 diabetic patients. Thus, predicting a consistent change in microbiome composition in response to fiber intake may simply involve too many variables.
A lack of consistency appears to be the only constant regarding dietary fiber’s influence on the gut microbiome.
The extent to which dietary fiber influences the gut microbiome is itself questionable. Different types of fiber are fermented differently, leading again to unpredictable gut microbiome alterations.4 Higher carbohydrate diets and higher fructooligosaccharide diets seem to increase Bifidobacteria, while other starches appear to enhance Bacteroides and Actinobacteria.9 However, the overall effect of fiber intake on the microbiome is inconsistent. Bacterial genomics may also affect how fiber enhances or inhibits bacterial growth. Different fiber structures coupled with different bacterial genomes may favor certain bacterial species over others.9 A lack of consistency appears to be the only constant regarding dietary fiber’s influence on the gut microbiome.
Clinical applications from the current study may be improved by looking at another analysis performed on this same TEDDY cohort, which evaluated whether probiotic supplementation and intake in the first year of life influenced the risk of islet cell autoimmunity later in childhood.10 The results showed a significantly decreased risk of islet cell autoimmunity in infants supplemented with probiotics between 0 and 27 days old as compared to those supplemented after 27 days old or not at all.
Ultimately, the current study calls into question whether dietary fiber intake alone can make a predictable positive alteration in the gut microbiome, leading to reduced risk of islet cell autoimmunity in genetically predisposed children. This and other studies have shown that the microbiome of type 1 diabetics is altered, but in an inconsistent fashion. Adding fiber to the diet does not seem to lead to predictable changes or improvement of type 1 diabetes development. Secondly, however, the role of probiotic flora is still important as demonstrated by the study on the TEDDY cohort that found a reduced risk of islet cell autoimmunity in infants taking probiotics early in life. It may be prudent to not depend on dietary alterations alone to change the microbiome, but to also supplement a genetically predisposed infant with probiotics soon after birth. Future studies should reevaluate the role of soluble fiber intake on type 1 diabetics, and perhaps should note the role of gluten-containing sources.