November 1, 2017

Bread and the Microbiome: A Personal Matter

Composition of stool flora may moderate responses
A randomized trial compares glycemic responses to industrially made white bread with responses to traditionally made whole grain sourdough and underscores the importance of genetic diversity in the gut microbiome.

Reference

Korem T, Zeevi D, Zmora N, et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metab. 2017;25(6):1243-1253.

Design

Randomized crossover trial

Participants

Twenty healthy participants, 9 men and 11 women, aged 18 to 70.

Study Parameters Assessed

Participants were randomized to 2 groups. One group consumed industrially produced white bread leavened with Saccharomyces cerevisiae (baker’s yeast), the other ate traditionally milled whole grain sourdough bread (the study did not specify which organisms the sourdough contained). Participants in each group consumed bread in the amount of 50 g available carbohydrate each morning for a week, plus additional consumption ad libitum of that type of bread throughout the day. Participants were instructed not to ingest other wheat products during this time. After a 2-week washout period, the groups switched for another week.

Primary Outcome Measures

Glucose metabolism (quantified by oral glucose tolerance test) and wakeup glucose levels; secondary outcome measures included blood chemistry, thyroid stimulating hormone (TSH), lipids, and blood pressure. Stool was collected at days 1, 6, 20, and 27 and analyzed for microbial species abundances.

Key Findings

No significant difference was seen in the primary outcome measures overall between the conventional white bread and whole grain sourdough bread consumption. In fact, great interpersonal variability was found in postprandial glucose response (PPGR) to the 2 types of bread—10 participants had lower glycemic response to white bread and 10 had lower response to sourdough.

Practice Implications

While the sample size and duration are small, this study is fascinating because it explores the relationship between the composition of the microbiome and glycemic response. While no significant difference was found overall in the glycemic response to the white vs whole grain sourdough bread, there was interpersonal variability. Some people consistently had a higher glycemic response to white, some to sourdough. When the makeup of stool flora was analyzed, each individual’s microbiome was predictive of their glycemic response. Also, each person’s microbiome remained relatively consistent throughout the testing period, regardless of which type of bread the person was eating.

Past studies have shown several factors influence PPGR to bread products. Steaming bread instead of baking, for example, decreases its glycemic index. The structure of the bread itself can also influence glycemic response: One study found that compact products such as flatbread and pasta showed a lower peak glucose and insulin response relative to bread with a porous structure.1 Longer proofing also increases porosity and therefore glycemic index.2 Adding or substituting fibers and grains such as inulin, oat fiber, and rye flour to traditional wheat bread can also decrease glycemic response.3-5 The data is mixed on whether sourdough leavening decreases glycemic response relative to yeasted bread. While all of this is very useful information for counseling patients on how to eat to support healthy blood sugar levels, this study opens up the possibility of taking our counseling one step further into the realm of individualization.

This new understanding of the microbiome creates an opportunity for clinicians to use data from patient stool samples to individualize their diet and supplement plan.

The connection between gut microbiota and blood sugar regulation, including metabolic syndrome and type 2 diabetes, has become more and more clear in recent years. The presence of certain bacteria in the gut seems to be associated with increased inflammation, adiposity, and insulin resistance, while others are associated with decreased inflammation and metabolic balance.6,7

A 2015 article in Diabetologia notes: “Lactobacillus species correlate positively with fasting glucose and glycosylated hemoglobin (HbA1c) levels whereas Clostridium species correlate negatively with fasting glucose, HbA1c, and insulin levels. A recent study suggests that a higher blood glucose concentration may be predicted by a reduction in the proportion of anaerobes, particularly Bacteroides.”8 In this study, 2 of the bacteria that informed the model for predicting glycemic response were Coprobacter fastidiosus (phylum Bacteroides) and Lachnospiraceae bacterium 3_1_46FAA (class Clostridia). In one rat study, Lachnospiraceae were also found to contribute to the onset of type 2 diabetes.9

This new understanding of the microbiome creates an opportunity for clinicians to use data from patient stool samples to individualize their diet and supplement plan. Unfortunately, though, at this time few if any of us are able to obtain full microbiome studies with relative abundances, and the tools for interpreting this data in a clinically relevant way do not yet exist on a large scale. On the other hand, blood sugar control is not only predicted by the presence or absence of certain species—it is related to the makeup of the microbiome as a whole. Decreased genetic diversity in the microbiota as well as an overall decrease in butyrate-producing bacteria are also associated with increased incidence of metabolic dysfunction.7,10 With this in mind, helping people understand how to eat and live in their environment in a way that increases exposure to many different microorganisms is a less daunting task, and relevant for any patient hoping to improve their glucose tolerance.

We are not yet able to individualize our diet plans to people’s microbiome, but we do have good tools for increasing its genetic diversity. While the gut flora remained mostly consistent for each person throughout this trial, other trials have of course shown dietary modifications that promote the growth of different types of bacteria. Prebiotics have been shown to decrease postprandial and fasting glucose and improve insulin sensitivity.10 For example, melanoidins, the product of the Maillard reaction that occurs when starch and protein are baked together and form the browned component of bread crust, have been found to decrease enterobacteria, which promotes inflammation, and increase bifidobacteria, which can improve glucose tolerance.11-13 Inulin and other polysaccharides such as fructooligosaccharide have also been shown to increase the production of bifidobacteria.14

The other good news is that general supplementation with commercially available probiotic formulations and fermented foods can also positively impact blood sugar. Meta-analyses of studies of people with type 2 diabetes and metabolic syndrome have shown that patients who supplemented with probiotics (of unspecified type) had lower fasting blood glucose as well as HbA1C.15-17 Probiotic supplementation has also been shown to increase insulin sensitivity and reduce inflammation. Interestingly, one meta-analysis showed the effects were greater with fermented milk products rather than encapsulated strains, indicating that the greater variety of bacteria in food sources is preferential.18,11 This supports the notion that greater diversity is better for blood sugar control. Going even further with this notion, several studies have suggested fecal transplantation as another viable therapy for diabetes.19,20

While the primary measures of this study did not show any significant overall difference in glycemic response to the different types of bread consumed, it used the data from each person’s microbiome to predict individual response. This gives us a new factor to consider when helping patients control their blood sugar. When we look at the balance and diversity of the flora in the gut, we can further individualize treatment to help patients improve and maintain metabolic health.

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References

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  2. Stamataki NS, Yanni AE, Karathanos VT. Bread making technology influences postprandial glucose response: a review of the clinical evidence. Br J Nutr. 2017;117(7):1001-1012.
  3. De Angelis M, Rizzello CG, Alfonsi G, et al. Use of sourdough lactobacilli and oat fibre to decrease the glycaemic index of white wheat bread. Br J Nutr. 2007;98(6):1196-1205.
  4. Scazzina F, Siebenhandl-Ehn S, Pellegrini N. The effect of dietary fibre on reducing the glycaemic index of bread. Br J Nutr. 2013;109(7):1163-1174.
  5. Yusof BN, Abd Talib R, Karim NA, et al. Glycaemic index of four commercially available breads in Malaysia. Int J Food Sci Nutr. 2009;60(6):487-496.
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  7. Gomes AC, Bueno AA, de Souza RG, Mota JF. Gut microbiota, probiotics and diabetes. Nutr J. 2014;13:60.
  8. Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia. 2015;58(10):2206-2217.
  9. Kameyama K, Itoh K. Intestinal colonization by a Lachnospiraceae bacterium contributes to the development of diabetes in obese mice. Microbes Environ. 2014;29(4):427-430.
  10. Barengolts E. Gut microbiota, prebiotics, and synbiotics in management of obestiy and prediabetes: review of randomized controlled trials. Endocr Pract. 2016;22(10):1224-1234.
  11. Helou C, Denis S, Spatz M, et al. Insights into bread melanoidins: fate in the upper digestive tract and impact on the gut microbiota using in vitro systems. Food Funct. 2015;6(12):3737-3745.
  12. Morales FJ, Somoza V, Fogliano V. Physiological relevance of dietary melanoidins. Amino Acids. 2012;42(4):1097-109.
  13. Borrelli RC, Fogliano V. Bread crust melanoidins as potential prebiotic ingredients. Mol Nutr Food Res. 2005;49(7):673-678.
  14. Krupa-Kozak U, Markiewicz LH, Lamparski G, et al. Administration of inulin-supplemented gluten-free diet modified calcium absorption and caecal microbiota in rats in a calcium-dependent manner. Nutrients. 2017;9(7).
  15. Li C, Li X, Han H, et al. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: a meta-analysis of randomized, controlled trials. Medicine (Baltimore). 2016;95(26):e4088.
  16. Akbari V, Hendijani F. Effects of probiotic supplementation in patients with type 2 diabetes: systematic review and meta-analysis. Nutr Rev. 2016;74(12):774-784.
  17. Samah S, Ramasamy K, Lim SM, et al. Probiotics for the management of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016;118:172-182.
  18. Gomes AC, Bueno AA, de Souza RG, et al. Gut microbiota, probiotics and diabetes. Nutr J. 2014;13:60.
  19. He C, Shan Y, Song W. Targeting gut microbiota as a possible therapy for diabetes. Nutr Res. 2015;35(5):361-367.
  20. de Groot PF, Frissen MN, de Clercq NC. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes. 2017;8(3):253-267.