November 2014 Issue

The Gut Microbiota — Is It a Novel Contributor to the Obesity and Diabetes Epidemics?
By Constance Brown-Riggs, MSEd, RD, CDE, CDN
Today's Dietitian
Vol. 16 No. 11 P. 22

Research shows strong associations between the types and amount of gut bacteria and these chronic conditions.

The medical community continues to combat the obesity and type 2 diabetes epidemics—metabolic disorders that genetics and lifestyle behaviors are believed to cause. To continue the battle against these conditions, recent research has begun to aim at a new target: the intestinal microbiota.

This article will review the literature on the gut microbiota and its role in obesity, insulin resistance, and type 2 diabetes, and discuss current methods for modulating the microflora, including nutrition and dietary modifications, that contribute to gut health.

Rising Epidemics
Despite advances in the treatment of obesity and type 2 diabetes, the 21st century continues to hold the distinction of the most diabetogenic era in human history. The number of American adults diagnosed with diabetes continues to soar. Obesity, which is considered a major risk factor for type 2 diabetes, also is rising at an ever-increasing rate. In fact, if obesity rates stay on their current trajectories, 44% of the US population will be obese by 2030, and the number of new type 2 diabetes cases may triple by that time. It's estimated that obesity could contribute to more than 6 million cases of type 2 diabetes in the next two decades.1

Management of diabetes involves controlling A1c, which assesses blood glucose control over the previous three months, blood pressure, and cholesterol levels. However, according to the National Institute of Diabetes and Digestive and Kidney Diseases, 47% of the 26 million people living with diabetes aren't meeting A1c goals, 49% have failed to control blood pressure, and 44% aren't meeting cholesterol treatment goals.

It's well established that weight loss of 5% to 10% of body weight can improve insulin sensitivity in overweight or obese individuals who are insulin resistant. However, even with weight loss, not all metabolic abnormalities such as lipid levels and blood pressure return to normal.2

Many medical experts believe that genetics and lifestyle behaviors cause obesity and type 2 diabetes. However, there's a growing body of research examining the role of the intestinal microbiota as a potential contributor to the diabetogenic era.

"Over the past 20 years, obesity and diabetes have increased tremendously," said Meghan Jardine, MS, MBA, RD, LD, CDE, during a presentation titled "What Have Gut Bugs Got to Do With Diabetes and Obesity," at the American Association of Diabetes Educators' annual meeting in August. Jardine, who's the associate director of diabetes nutrition education for the Physicians Committee for Responsible Medicine, a Washington, D.C.-based nonprofit organization dedicated to promoting preventative medicine, said human genes haven't changed over the past 20 years, so that can't fully account for the obesity and diabetes epidemics. "Many scientists don't believe the changes in our diet and physical activity can [fully] account for the rising epidemic either," she said. "Scientists believe it's the gut bacteria—the microbiota—that have changed and play a role in obesity, obesity-related inflammation, and insulin resistance, which leads to type 2 diabetes."

Gut Bacteria and Health
Microbiota are the normal bacteria found in the human body. These bacteria are found in the surface or deep layers of many tissues including the skin (skin microbiota), the mouth (oral microbiota), the vaginal tract (vaginal microbiota), and the gut or intestinal tract (gut or intestinal microbiota). The most densely populated and diverse microbiota are found in the intestines.3 In fact, there are 10 trillion to 100 trillion bacteria and other microscopic organisms living in our gut, with each person hosting at least 160 different species.4

Other research suggests an interrelation between the different microbiota species that may work together for the benefit of the human body. Experts believe that a wide diversity of bacteria in the gut is beneficial. "We're just now starting to understand the role [the microbiota species] collectively play in our health, including diabetes, obesity, heart disease, and even cancer," says Kristi L. King, MPH, RDN, CNSC, LD, a senior pediatric dietitian at Texas Children's Hospital and spokesperson for the Academy of Nutrition and Dietetics. "Just as your kidneys are essential for creating urine, we're seeing how essential these bugs are for keeping us healthy. We know that without them, or [with] a significant imbalance, our health could suffer greatly."

Many factors shape our microbiota as it evolves throughout our lives. "A baby's gut is sterile at birth, and the diversity of microbiota depends on how the child was delivered," Jardine said. "Vaginal birth compared to cesarean section results in more diverse microbiota. Infants who are breast-fed have a greater diversity of microbiota than those fed infant formula. Nutrition, genetics, antibiotic use, diabetes, and even our environment shape our microbiota."

According to a monograph series called Probiotics, Prebiotics and the Gut Microbiota by the International Life Sciences Institute, "An increased proportion of Bifidobacteria and Lactobacilli is thought to represent a 'healthier' microbial composition."5

Chris Kafity, RN, BSN, a gastrointestinal nurse and administrator at Bay Area Gastroenterolgy in Norwalk, Ohio, and copresenter of "What Have Gut Bugs Got to Do With Diabetes and Obesity," agrees: "A healthy adult gut will have greater richness and diversity of bacterial species, and the host will exhibit better nutritional status, fewer comorbidities, and greater overall health."

Altered Microbiota
On the other hand, recent studies have found an association between diabetes and obesity and fewer but more specific bacterial species. "Obesity is associated with reduced microbiota diversity, a higher ratio of Firmicutes to Bacteroidetes, and depletion of Bifidobacteria," said Jardine, who attributes these changes to a high-fat diet.

In animal models, dietary changes altered the ratio of Bacteroidetes and Firmicutes. In fact, studies have shown that when mice are fed a high-fat Western diet there's an increase in Firmicutes and a decrease in Bacteroidetes.6 Yalcin Basaran, MD, an endocrinologist at Gulhane Military Medical Academy School of Medicine in Ankara, Turkey, presented findings from his research on gut microbiota and the link to type 2 diabetes and obesity at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago. His study included 27 severely obese adults with a BMI over 35 kg/m2 as well as 26 adults with newly diagnosed type 2 diabetes and 28 healthy controls. Fecal analyses showed that several common types of gut bacteria were present at lower levels in the obese and diabetes patient groups, compared with healthy controls. These reductions ranged from 4.2% to 12.5% in the obese subjects and 10% to 11.5% in the diabetes patients.4

Basaran also found that bacterial counts related to certain metabolic variables. BMI and hemoglobin A1c influenced levels of Firmicutes, the most common gut bacteria species. Waist circumference and hemoglobin A1c was linked with levels of Bifidobacteria, a type of Actinobacteria; and both weight and fasting blood glucose was associated with Clostridium leptum counts.4 "Further studies should be carried out to elucidate if the gut microbial changes are a cause or effect of metabolic diseases," Basaran said in a press release.

Modulating the Gut Environment
Basaran and other scientists believe that manipulation of the gut microbiota could offer a new approach in the management of obesity and type 2 diabetes.6 Three modulators of gut microbiota—prebiotics, probiotics, and synbiotics—continue to garner interest as novel therapeutic agents.

Prebiotics
Prebiotics are described as nondigestible substances that stimulate the growth or activity of potentially beneficial gut microbiota. The International Scientific Association of Probiotics and Prebiotics defines a prebiotic as "a selectively fermented ingredient that results in specific changes, in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health."5

Over the past 19 years, there has been a wealth of research on the concept of modulating gut microbiota with prebiotics. Studies show that prebiotics can increase the proportion of Bifidobacteria and Lactobacilli.5 Bifidobacteria is associated with improved health by inhibiting the growth of pathogenic bacteria, modulating the immune system, producing digestive enzymes, repressing the activities of rotaviruses, and restoring microbial integrity of the gut microbiota following antibiotic therapy.7

Most animal and human studies used inulin-type fructans as the preferred prebiotic. Study results showed that daily prebiotic consumption reduced appetite, lowered body weight or fat mass, altered gut peptide levels in blood, and improved glucose tolerance.5 Inulin is naturally occurring in foods such as artichoke, asparagus, chicory, garlic, and onion. However, the amount of inulin in these foods doesn't reach the 5 to 8 g daily requirement needed to modulate gut microbiota. So functional food developers add inulin to products that are frequently consumed such as cereals, candy, pastries, biscuits, yogurts, and table spreads.7

The benefits of a high-fiber diet that includes whole grains, vegetables, fruits, and legumes are well established. As research on fibers with prebiotic properties continues, they can be recommended as part of daily fiber intake; however, it's important to encourage consumption of fiber from a variety of sources.

Probiotics
Probiotics are live bacteria that are either the same as or similar to the bacteria found naturally in the human body and may be beneficial to health. They're often referred to as "good bacteria" or "helpful bacteria." The Food and Agriculture Organization and the World Health Organization define probiotic bacteria as "live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host."

Previous research on the effects of probiotics on the characteristics of type 2 diabetes largely involved animal studies. However, in a 2014 literature review, Gomes and colleagues found an emerging body of clinical evidence showing that probiotics reduce inflammation, oxidative stress, and intestinal permeability, which can increase insulin sensitivity and reduce autoimmune response.8 For example, in a double-blinded clinical study, individuals with type 2 diabetes experienced reduced fasting glucose and HbA1c levels, and increased total antioxidant capacity after consuming one yogurt daily containing Lactobacillus acidophilus for six weeks.8

In another double-blinded, placebo-controlled, randomized trial, females with type 2 diabetes given 100 mL of a shake containing Lactobacillus acidophilus, Bifidobacterium bifidum, and fructooligosaccharides twice daily exhibited a reduction in blood glucose levels.8 The shake in this study contained both probiotic bacteria and prebiotic saccharides, forming a synbiotic. A synbiotic is formed when a probiotic and prebiotic are combined. Studies have shown that every probiotic benefits from a select number of carbohydrates. When prebiotics are selected based on their ability to stimulate the growth of the probiotic part, the effects of the probiotic are enhanced.

Many products sitting on store shelves carry the label "probiotic," but all too often they don't meet qualifying criteria for probiotics, such as defined contents, viability at the end of shelf life, and evidence of health benefits. In an expert consensus document published in June 2014, the International Scientific Association for Probiotics and Prebiotics recommended that the term "probiotic" be used only on those products that actually deliver live microorganisms with suitable viable counts of specific strains with an expectation of delivering health benefits. Since there's no evidence of a health benefit associated with fermented foods the panel also recommends that these foods be kept outside the probiotic framework.

Guiding Patients
"We still have a ways to go in gut microbiota research, but what we've seen so far is quite interesting and promising in all aspects of health," King says. "As we learn more about the gut microbiota, we'll be able to individually tailor diets to help minimize or prevent symptoms of chronic disease." In the meantime, nutrition intervention strategies should emphasize healthful plant-based eating patterns that include fermented foods such as yogurt, kefir, buttermilk, sourdough bread, and kimchee.

— Constance Brown-Riggs, MSEd, RD, CDE, CDN, is past national spokesperson for the Academy of Nutrition and Dietetics, specializing in African American nutrition, and author of The African American Guide to Living Well With Diabetes and Eating Soulfully and Healthfully With Diabetes.

 

References
1. Trust for America's Health. F as in Fat: How Obesity Threatens America's Future 2012. http://healthyamericans.org/report/100/. Accessed September 14, 2014.

2. Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73-83.

3. Owyang C, Wu GD. The gut microbiome in health and disease. Gastroenterology. 2014;146(6):1433-1436.

4. Gut microbe levels are linked to type 2 diabetes and obesity. Endocrine Society website. https://www.endocrine.org/news-room/current-press-releases/gut-microbe-levels-are-linked-to-type-2-diabetes-and-obesity. Accessed September 14, 2014.

5. Binns N. International Life Sciences Institute. Probiotics, Prebiotics and the Gut Microbiota. http://www.ilsi.org/Europe/Publications/Prebiotics-Probiotics.pdf.  Accessed September 14, 2014.

6. Kootte RS, Vrieze A, Holleman F, et al. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab. 2012:14(2):112-120.

7. Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr. 2007;137(11):2503S-2506S.

8. Gomes AC, Bueno AA, de Souza RGM, Mota JP. Gut microbiota, probiotics and diabetes. Nutrition Journal. 2014;13:60.

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