The fight against type 2 diabetes may soon improve thanks to a pioneering high-fiber diet study led by a Rutgers University-New Brunswick professor.

Promotion of a select group of gut bacteria by a diet high in diverse fibers led to better blood glucose control, greater weight loss and better lipid levels in people with type 2 diabetes, according to research published today in Science.

The study, underway for six years, provides evidence that eating more of the right dietary fibers may rebalance the gut microbiota, or the ecosystem of bacteria in the gastrointestinal tract that help digest food and are important for overall human health.

“Our study lays the foundation and opens the possibility that fibers targeting this group of gut bacteria could eventually become a major part of your diet and your treatment,” said Liping Zhao, the study’s lead author and a professor in the Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences at Rutgers University-New Brunswick.

Type 2 diabetes, one of the most common debilitating diseases, develops when the pancreas makes too little insulin — a hormone that helps glucose enter cells for use as energy — or the body doesn’t use insulin well.

In the gut, many bacteria break down carbohydrates, such as dietary fibers, and produce short-chain fatty acids that nourish our gut lining cells, reduce inflammation and help control appetite. A shortage of short-chain fatty acids has been associated with type 2 diabetes and other diseases. Many clinical studies also show that increasing dietary fiber intake could alleviate type 2 diabetes, but the effectiveness can vary due to the lack of understanding of the mechanisms, according to Zhao, who works in New Jersey Institute for Food, Nutrition, and Health at Rutgers-New Brunswick.

In research based in China, Zhao and scientists from Shanghai Jiao Tong University and Yan Lam, a research assistant professor in Zhao’s lab at Rutgers, randomized patients with type 2 diabetes into two groups. The control group received standard patient education and dietary recommendations. The treatment group was given a large amount of many types of dietary fibers while ingesting a similar diet for energy and major nutrients. Both groups took the drug acarbose to help control blood glucose.

The high-fiber diet included whole grains, traditional Chinese medicinal foods rich in dietary fibers and prebiotics, which promote growth of short-chain fatty acid-producing gut bacteria. After 12 weeks, patients on the high-fiber diet had greater reduction in a three-month average of blood glucose levels. Their fasting blood glucose levels also dropped faster and they lost more weight.

Surprisingly, of the 141 strains of short-chain fatty acid-producing gut bacteria identified by next-generation sequencing, only 15 are promoted by consuming more fibers and thus are likely to be the key drivers of better health. Bolstered by the high-fiber diet, they became the dominant strains in the gut after they boosted levels of the short-chain fatty acids butyrate and acetate. These acids created a mildly acidic gut environment that reduced populations of detrimental bacteria and led to increased insulin production and better blood glucose control.

The study supports establishing a healthy gut microbiota as a new nutritional approach for preventing and managing type 2 diabetes.

Story Source: ScienceDaily

Journal Reference:

1. Liping Zhao, Feng Zhang, Xiaoying Ding, Guojun Wu, Yan Y. Lam, Xuejiao Wang, Huaqing Fu, Xinhe Xue, Chunhua Lu, Jilin Ma, Lihua Yu, Chengmei Xu, Zhongying Ren, Ying Xu, Songmei Xu, Hongli Shen, Xiuli Zhu, Yu Shi, Qingyun Shen, Weiping Dong, Rui Liu, Yunxia Ling, Yue Zeng, Xingpeng Wang, Qianpeng Zhang, Jing Wang, Linghua Wang, Yanqiu Wu, Benhua Zeng, Hong Wei, Menghui Zhang, Yongde Peng, Chenhong Zhang. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 2018; 359 (6380): 1151 DOI: 10.1126/science.aao5774

Stanford researchers found that manipulating the gut microbe Clostridium sporogenes changed levels of molecules in the bloodstreams of mice and, in turn, affected their health.

Here’s some food for thought: When you lick your Thanksgiving plate clean this week, you’re not just feeding yourself; you’re also providing meals to the trillions of microbes that live in your gut. And if your dinner includes turkey, a notoriously rich source of the amino acid tryptophan, the gut bacterium Clostridium sporogenes will have the job of breaking down that tryptophan. Then the molecules that are produced by the microbe will flow into your bloodstream in the same way a prescription drug might, interacting with your immune system and changing the biology of the intestines.

Stanford University School of Medicine researchers have used mice to demonstrate how gut bugs could be bioengineered to produce possibly therapeutic changes in the body.

A paper describing their efforts was published online Nov. 22 in Nature. Justin Sonnenburg, PhD, associate professor of microbiology and immunology, and Michael Fischbach, PhD, associate professor of bioengineering, share senior authorship. The lead author is Dylan Dodd, MD, PhD, instructor in pathology.

When the researchers blocked the ability of C. sporogenes to break down tryptophan in mice, levels of certain molecules in their bloodstreams changed. Moreover, the researchers saw physiological changes to the mice’s immune systems and intestines.

“This is a vivid example of not only how the microbiome is affecting things all over your body, but of how we can leverage that to improve health,” said Sonnenburg, using a term for the collection of microbes living on or inside an animal, or in a particular part.

Improving health from the inside

Over the past 15 years, researchers have shown that the composition of a person’s gut microbiome can alter their risk for all sorts of health problems, from diabetes and heart disease to allergies and depression. One reason these tiny microbes have such an outsized effect: They can produce molecules known as metabolites that enter the bloodstream and circulate throughout the body. Pinning down exactly which molecules are produced by which bacteria, however, and how to alter their levels to change health, has been challenging.

Previous studies have shown that just a few bacteria, including C. sporogenes, can break down tryptophan and produce the metabolite known as indolepropionic acid. Studies have also hinted that IPA helps fortify the intestinal wall, letting fewer molecules leak through.

In the new work, the researchers first detailed exactly how C. sporogenes produces IPA from tryptophan. They identified a handful of other compounds also produced in the process — 12 metabolites in total, nine of which can accumulate in the blood and three of which are produced only by bacteria. Then, the researchers pinpointed for the first time the genes that C. sporogenes requires for the breakdown of tryptophan and metabolism of the resulting molecules. A gene called fldC, they showed, is required for the production of IPA.

Next, the team gave germ-free mice either wild-type C. sporogenes—with the ability to produce IPA—or a version of the bacteria that lacked fldC. In mice that received the wild-type bacteria, levels of IPA in the bloodstream were around 80 micromolar; in mice that received the engineered version of the bacteria, IPA was undetectable.

Finally, they looked at how altering the levels of IPA affected the mice. Mice with undetectable IPA, they found, had higher levels of immune cells, including neutrophils, classical monocytes and memory T cells. This suggested activation of two branches of the immune system—the innate and adaptive immune system. In addition, the mice with the engineered version of C. sporogenes had more permeable intestines, a defect which is often seen in gut diseases, including inflammatory bowel disease.

Targeting microbes

If the results hold true in humans, said Sonnenburg, it could point toward a new paradigm for treating some diseases: rather than give a compound, such as IPA, physicians may one day be able to tweak levels of bacteria to affect levels of metabolites. For instance, it might be possible to treat inflammatory bowel disease by boosting levels of C. sporogenes and ensuring patients eat enough tryptophan.

“This gives us a specific example of how we can target individual microbes and pathways in the gut to change a person’s health,” Dodd said. “And this is just one example of hundreds or thousands that are likely out there.”

The group next plans to study C. sporogenes and IPA levels in mice with more complex gut microbiomes—rather than germ-free mice—and begin tracking down other metabolites produced by the gut microbes that may have health effects.

“While providing a stunning example of how a single gut microbe, and a single gene within that microbe, can impact host health, IPA is just the tip of the iceberg,” said Fischbach, “The possibility to positively impact human health through microbiome-produced chemicals is tremendous, and we are poised to take big strides and make this a reality.”

Other Stanford authors are Matthew Spitzer, PhD, a former graduate student; graduate students William Van Treuren and Bryan Merrill; postdoctoral scholar Andrew Hryckowian, PhD; life science researcher Steven Higginbottom, PhD; Gary Nolan, PhD, professor of microbiology and immunology; adjunct faculty member Anthony Le; and Tina Cowan, PhD, professor of pathology.

Story Source: medicalxpress.com

More information: A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites, Nature (2017). nature.com/articles/doi:10.1038/nature24661

Weizmann Institute researchers report the results of a comprehensive, randomized trial in 20 healthy subjects comparing differences in how processed white bread and artisanal whole wheat sourdough affect the body.

When we eat, we do not just take in nutrients – we also consume a significant quantity of bacteria. The body is faced with the challenge of simultaneously distributing the ingested glucose and fighting these bacteria. This triggers an inflammatory response that activates the immune systems of healthy individuals and has a protective effect, as doctors from the University and the University Hospital Basel have proven for the first time. In overweight individuals, however, this inflammatory response fails so dramatically that it can lead to diabetes.

It is well known that type 2 diabetes (or adult-onset diabetes) leads to chronic inflammation with a range of negative impacts. A number of clinical studies have therefore treated diabetes by impeding the over-production of a substance involved in this process, Interleukin-1beta (IL-1beta). In diabetes patients, this messenger substance triggers chronic inflammation and causes insulin-producing beta cells to die off.

Activation of the immune system

This inflammation does have some positive aspects, however, as was recently reported in the journal Nature Immunology by researchers from the Department of Biomedicine at the University and the University Hospital Basel. In healthy individuals, short-term inflammatory responses play an important role in sugar uptake and the activation of the immune system.

In their work, Professor Marc Donath, Head of the Department of Endocrinology, Diabetes and Metabolism at the University Hospital Basel and his research team demonstrate that the number of macrophages (a type of immune cell) around the intestines increases during meal times. These so-called “scavenger cells” produce the messenger substance IL-1beta in varying amounts, depending on the concentration of glucose in the blood. This, in turn, stimulates insulin production in pancreatic beta cells. The insulin then causes the macrophages to increase IL-1beta production. Insulin and IL-1beta work together to regulate blood sugar levels, while the messenger substance IL-1beta ensures that the immune system is supplied with glucose and thus remains active.

Bacteria and nutrients

According to the researchers, this mechanism of the metabolism and immune system is dependent on the bacteria and nutrients that are ingested during meals. With sufficient nutrients, the immune system is able to adequately combat foreign bacteria. Conversely, when there is a lack of nutrients, the few remaining calories must be conserved for important life functions at the expense of an immune response. This may go some way towards explaining why infectious diseases occur more frequently in times of famine.

Story Source: ScienceDaily

More information: doi:10.1038/ni.3659