Nutrition Considerations for Microbiota Health in Diabetes

Eating Patterns and Food Groups

Dietary habits play a significant role in shaping the microbiota, providing substrates that determine the assortment of metabolites produced. Many researchers have suggested that a Western eating pattern may have altered the genetic composition and metabolic activity of the human microbiome, significantly contributing to modern diseases (15). Eating patterns higher in whole grains, fruits, vegetables, and legumes have been found to induce a more diverse microbial population, increasing the abundance of protective species while reducing the abundance of pathobionts and the production of inflammatory factors (16). High-fat, animal-based diets are associated with a low gene count and a higher abundance of bile-tolerant bacteria because fat causes more bile acids to be secreted (15).

Microbial metabolism of fat and protein in the colon can result in the formation of toxic metabolites such as ammonia, phenolic and indole compounds, amines, and sulfides (9,17). Carnitine and choline found in red meat and eggs are metabolized by gut microbes to produce trimethylamine, which is absorbed and further metabolized in the liver to trimethylamine-N-oxide (TMAO), a metabolite linked to the formation of atherosclerotic lesions (16). A recent study found that TMAO production after an L-carnitine challenge was dependent on microbiota composition. Comparing participants following a vegan, vegetarian, or omnivore dietary pattern, both vegan and vegetarians had significantly lower plasma TMAO levels compared to omnivores (16).

Significant differences in terms of microbial composition and health have been demonstrated between plant-based or agrarian eating patterns and Western eating patterns. De Filippo et al. (18) compared the fecal microbiota of 14 young children (ages 1–6 years) living in rural Africa and consuming a high-fiber, low-fat diet to that of 15 children of matched age from Europe and consuming a Western eating pattern. The African children’s diet was high in cereals (millet and sorghum), legumes (mostly black-eyed peas), and vegetables. They consumed little meat other than occasional chicken or termites during the rainy season. In contrast, the European children’s diet was higher in animal protein, sugar, starch, and fat and had almost half the amount of dietary fiber found in the African children’s diet. The African children’s microbiota was significantly higher in Bacteroidetes and lower in Firmicutes compared to the European children. A higher ratio of Firmicutes to Bacteroidetes is associated with obesity and diabetes. The African children also had an abundance of the genera Prevotella and Xylanibacter, both having significant anti-inflammatory effects, which were completely lacking in the European children. The European children’s microbiota had an abundance of the genus Bacteroides, consistent with a high-fat, high-meat diet. The African children’s microbiome was more genetically diverse and contained a lower prevalence of the pathobiont Enterobacteriaceae and a higher amount of short-chain fatty acid (SCFA) production compared to the European children.

An analysis of 153 subjects, self-declared as vegan, vegetarian, or omnivore and all following a Mediterranean diet revealed marked variations in the microbial content and metabolites produced from each eating pattern (17). The vegan group scored highest in the adherence to the Mediterranean diet, evaluated by the Healthy Food Diversity (HFD) score, indicating a higher intake of fruits, legumes, and vegetables. Higher HFD scores were associated with beneficial microbial profiles, with a greater abundance of Rosburia, Lachnospira, and Prevotella and a significantly higher production of SCFAs. There are significantly higher levels of L-Ruminococcus, a genus assigned to the Lachnospiraceae family, as well as higher levels of urinary TMAO in the group consuming the most protein-rich animal foods and dietary fat.

The two studies discussed above provide evidence that long-term adherence to a high-fiber, plant-based eating pattern can provide benefits to the composition of the microbiota.

A small intervention study using a strict vegetarian diet (72% carbohydrate, 16% protein, and 12% fat) for 1 month with six subjects with diabetes or hypertension demonstrated both clinical and microbial improvements (19). There were significant reductions in body weight, triglycerides, LDL cholesterol, and A1C and improvements in fasting and postprandial glucose levels. The composition and metabolites produced by the microbiota were also altered. The strict vegetarian diet resulted in a decrease in the ratio of the phyla Firmicutes to Bacteroidetes, a reduction in pathobionts, and specifically Enterobacteriaceae, a known pro-inflammatory species. Increases in commensal bacteria Bacteroides fragilis, Prevotella, Lachnospiraceae (protects against C. difficile), and Ruminococcaceae were noted, as well as reductions in inflammatory markers.

A longer-term intervention improved insulin sensitivity for 20 obese men with known coronary heart disease randomly assigned to either a Mediterranean diet or a low-fat, high-complex carbohydrate (LFHC) diet for 1 year. There was a reported increase in the abundance of Roseburia genus and F. prausnitzii for the Mediterranean diet and LFHC diet, respectively. The authors concluded that both eating patterns, which focus on an increase in fruits and vegetables, produced improvements in the microbiota, potentially reducing the risk of type 2 diabetes (20).

Epidemiological studies consistently demonstrate that dietary fiber, particularly whole-grain fiber, intake is inversely associated with type 2 diabetes and cardiovascular disease and has a beneficial impact on body weight and longevity (21–23). In a prospective, observational study, a high intake of cereal fiber was associated with a 33% lower risk of diabetes compared to a low intake. The authors proposed that whole grains may offer protection by increasing SCFA production and, in turn, their effect on increasing hepatic insulin sensitivity (22). A recent meta-analysis provided a quantitative estimation that consuming three servings of whole-grain foods per day would offer a 20% relative reduction in risk of type 2 diabetes compared to consuming a half serving (23). Other nutrients that contribute to health and are present in whole grains include minerals, vitamins, phytochemicals, phenolic compounds, lignans, and phytic acid (23). Human studies have demonstrated significant increases in the abundance of Bifidobacterium species and Lactobacillus/Enterococcus in participants consuming whole-grain wheat cereal (24). Other studies produced similar improvements with whole-grain barley flakes and whole-grain brown rice flakes (24).

Other foods and beverages that have improved the microbiota in human studies include red berries (specifically blueberries) that are high in anthocyanins, almonds and pistachios, apples and bananas, and red wine (24). There has been negligible research on vegetables and legumes in terms of modulating the microbiota (24).

Prebiotics

A prebiotic is defined as “a selectively fermented ingredient that allows specific changes, both in composition and/or activity, in the gut microbiota that confers health benefits upon host well-being and health” (3,9,25). Table 1 provides the criteria used to classify prebiotics. Prebiotics are carbohydrate compounds, mostly oligosaccharides, that resist digestion in the small intestine and are fermented in the colon, producing SCFAs and the growth of beneficial bacteria, specifically Bifidobacterium, Lactobacillus (25), F. prausnitzii, A. muciniphila (14), and Rominoccoccus bromii (9).

Humans have been consuming prebiotics since prehistoric times. In fact, archaeological evidence of well-preserved coprolites has demonstrated that a typical adult male hunter-gatherer consumed 135 g inulin per day (25). The primary forms of dietary prebiotics include resistant starch, nonstarch polysaccharides, and nondigestible oligosaccharides (9,25,26). Fermentation of 100 g prebiotic can produce 20 g beneficial bacteria (25). Table 2 lists dietary source of prebiotics and their documented health outcomes.

Prebiotics improve satiety, decrease food intake, and are associated with reduced postprandial glucose levels (6,14). The mechanisms are not entirely understood, but these effects may be due to the production of SCFAs, which are ligands for G-protein–coupled receptors present on L-cells promoting the secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) (3,6). Studies have demonstrated that prebiotic supplementation of 5–20 g prebiotic per day has produced changes in microbiota composition, increasing GLP-1 and PYY levels, reducing ghrelin, resulting in reduced hunger and energy intake and reduced postprandial glucose levels (3,12,27,28). Prebiotic supplementation with an inulin/oligofructose mix in obese women led to an increase in Bifidobacterium and F. prausnitzii, two bacteria reported to be reduced in type 2 diabetes (29). There was a marked reduction in serum LPS levels, reducing metabolic endotoxemia. SCFAs provide a direct energy source for colonocytes, resulting in increased thickness of the intestinal wall and reducing the risk of bacterial translocation (30). Other nutritional benefits of plant fermentation include the release of phytochemicals with anti-inflammatory and antioxidant properties and an enhanced bioavailability and uptake of minerals, including calcium, magnesium, zinc, and possibly iron (9,25,31). SCFA production reduces colonic pH, reducing the growth of pathogenic bacteria and their toxic metabolites (25). Table 3 lists the beneficial effects of SCFAs.

Probiotics

Probiotics are “live microorganisms [that], when administered in adequate amount, provide a health benefit on the host” (25,32). Popular probiotic strains belong to the genera Bifidobacterium and Lactobacillus and include yeasts such as Saccharomyces boulardii (7). Fermentation of foods has been used for centuries to increase the shelf life and enhance the nutrition quality and flavor of foods (32).

Although the research has not been consistent, some probiotics studies involving healthy volunteers have shown reductions in body fat and improvements in insulin sensitivity. There have been fewer well-controlled trials involving individuals with diabetes (14). A review that included six clinical studies on individuals with diabetes found a reduction in inflammatory responses and oxidative stress, improved insulin sensitivity, and reduced fasting glucose with various probiotic dosages (33). However, further investigations are warranted to determine whether probiotics could be used for the prevention and treatment of diabetes.

Specific strains and dosage recommendations (or serving sizes of fermented foods) for diabetes have not yet been determined and therefore are not recommended for clinical practice. Interestingly, probiotics account for the largest share of the rapidly expanding functional food market (32). Table 4 and Table 5 list the criteria for probiotic classification and dietary sources of probiotics, respectively.