The Link Between Type 2 Diabetes and the Gut Microbiome
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By Colleen Cutcliffe, PhD and The Pendulum Team
The gut microbiome is an ecosystem that exists deep within our gut and is intimately linked to our health. Like any ecosystem, the gut microbiome is resistant and resilient to change, but at the same time highly adaptable to new challenges. These gut microbial changes can either help or hurt us. Decades of research have shown us that changes in our microbiome that increase the presence of specific types of bacteria may help protect us from conditions like type 2 diabetes. On the other hand, a reduced abundance of certain gut microbes can result in an increased likelihood of developing these common metabolic diseases, like type II diabetes.17
Fortunately, there are steps you can take to encourage the growth of the beneficial bacteria and reduce the risk of diabetes. Overwhelming evidence supports a role of a healthy diet in this risk reduction. In addition, there is recent evidence (study) to support the concept that certain probiotics can also be of benefit.
The Relationship Between Type 2 Diabetes and The Gut Microbiome
There is a close relationship that exists between the gut microbiome and human health. Both are capable of influencing the other in ways that we don’t fully understand yet. However, research over the past few decades, carried out using everything from Petri-dishes to mice to humans, has uncovered a particularly strong link between the development of type 2 diabetes and the bacteria inside your gut.
The gut microbiome is home to trillions of individual bacteria, each belonging to one of hundreds of potential species. It is often described as being similar to rainforests or tide pools—ecosystems where many diverse species co-exist in some state of competition, synergy and harmony. And, like these other ecosystems, the gut microbiome is highly resilient and resistant to change, and at the same time highly adaptable. Such changes are not always of benefit to our gut and our metabolic health.
What species of bacteria live in your gut depend on several factors including:
- Your diet
- Your exercise levels and routines
- Medicine you may be taking
- Travel to foreign countries
- Your stress levels
- Your sleep habits
- Your genetics
Because of this, the exact composition of any one person’s microbiome can change over time and differs substantially from another person’s.1
In many instances, these interindividual differences have no effect on your health. But other times, when the relative abundance of specific types of bacteria are reduced, it could increase the risk for type 2 diabetes1.1,2,3 For example, multiple studies have found that species belonging to the genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia, and Roseburia were often reduced in people who have type 2 diabetes.1 The reduced abundance of some of these species in people with type 2 diabetes suggests that they may play an important role in protecting us from various metabolic conditions, such as diabetes and obesity.
How does the lack of certain strains of gut bacteria lead to type 2 diabetes?
The types of bacterial species that are frequently reduced in people with type 2 diabetes tend to be ones that do one of four things:
- Produce the beneficial short chain fatty acid butyrate
- Strengthen the gut mucosal lining
- Prompt the release of certain metabolic hormones
- Reduce inflammation in the gut
Each of these interrelated functions are important to our health, and the reduction in the abundance of bacteria responsible for carrying out these activities can leave a person vulnerable to several conditions, including type 2 diabetes.
Many of the strains of bacteria that are reduced in people with type 2 diabetes are involved in the production of the short chain fatty acid butyrate — an important, multifunctional molecule that can be used for energy by the cells that line the colon (colonocytes), can act like a hormone in certain contexts,4 and has been shown to have a number of far-reaching, beneficial effects on the human body.
Butyrate is produced in the last part of the small and in the large intestine as a breakdown product of dietary fiber. Dietary fibers are complex molecules that human cells are unable to break down and absorb. Were it not for some species of bacteria in the gut, dietary fibers would go right through us without absorption. Fortunately, though, there are bacteria in the gut microbiome that use fiber contained in all plant-based foods—they thrive on a fiber rich diet and consume it by breaking it down into health promoting molecules such as butyrate.5
Microbial derived butyrate serves many vital functions, among them the nutritional support of the cells lining the colon, the production and release of serotonin and satiety hormones in the gut, and the release of a hormone known as GLP-1.1,5,6,7 GLP-1 is called an incretin, a molecule that stimulates the release of insulin and at the same time plays a major role in generating a sensation of fullness and satiety. As insulin increases, cells throughout the body start to take up sugar from the bloodstream, lowering blood sugar levels in the process. This process is a critical part of maintaining a healthy blood sugar level and preventing long-term damage that’s associated with high blood sugar levels.1,7
Butyrate is also known to reduce inflammation by several mechanisms: it supports a tight gut barrier, separating gut microbes from immune cells in the gut, and it decreases the activation of the gut associated immune system, which is often seen in patients with metabolic syndrome and type II DM.4
If butyrate is so important, why can’t you just take a butyrate supplement and call it a day?
You could try and address some symptoms of type 2 diabetes by taking supplements that are specifically designed to deliver butyrate to the colon.8
However, such an approach would be similar to buying a box of nails and a hammer instead of hiring a carpenter—the butyrate delivered through the supplement may be temporarily effective, but it is only a temporary solution and one that fails to compensate for the many different roles that gut bacteria play.
Additionally, when bacteria produce butyrate, they do so while occupying many different locations in the gut. This means that butyrate can be moved closer to, or further from, the cells lining the gut depending on where the butyrate-producing bacteria are. By producing butyrate in various locations, the body can ensure that the right cell types get this precious nutrient.
Butyrate supplements, however, like many available probiotics are hard-pressed to replicate these dynamics. Instead, they deliver the butyrate in an even and linear fashion that allows for any cell capable of using butyrate to do so.
As a result, the amount of butyrate available to the cells that need them, and the amount of butyrate that is absorbed, can be significantly different when taking supplements as opposed to making the butyrate in-house with butyrate-producing bacteria. Finding ways to replenish the bacteria that are so reduced in abundance in people with type 2 diabetes has several advantages. Restoring the missing bacteria may help reduce the leakiness of the gut while also providing an internal source of butyrate.
Regulating the mucin lining and preventing “leaky gut syndrome”
A gut that is described in the lay media as “leaky” is one where the cell- and mucus-barrier that lines our intestine is more porous and less able to prevent microbes from passing into the bloodstream.
The types of bacteria that are often reduced in people with type 2 diabetes are known to help maintain a healthy gut barrier. They do this through several different mechanisms. One way these bacteria contribute to the gut barrier is by helping to replenish the mucosal layer.
Akkermansia muciniphila, for example, is known to live in the mucosal layer and to feed on the mucus. As it does this, it releases some molecules that are sensed by cells in the gut which respond by producing more mucus. In this way, akkermansia muciniphila helps the gut keep a fresh and healthy mucus layer.1,9
Another way bacteria contributes to a healthy gut is by producing signaling molecules, like butyrate. These signaling molecules promote several functions in the cells that form a tight barrier.1 Butyrate is known to support the production of tight-junction proteins in these barrier cells.1 With a reduction in tight connections between these cells, gaps form between them which allows microbes to cross between cells, come in contact with the gut associated immune system, and enter the systemic circulation, a phenomenon called metabolic endotoxemia.1
What specific strains of bacteria affect type 2 diabetes?
Many types of bacteria have been suggested to have a positive role to play in protecting us from type 2 diabetes.1,2,3 Details vary from study to study, likely because of differences in medication use, environment, diet, and exercise habits among participants in these studies. However, some groups of bacteria have been reliably shown to be protective.
Akkermansia muciniphila (WB-STR-0001) is one of them. As mentioned above, this strain of bacteria plays a critical role in supporting a healthy gut lining and in reducing gut inflammation, both of which favor healthy blood sugar levels.
Eubacterium hallii (WB-STR-0008) is a butyrate-producing bacteria. Many people with type 2 diabetes are deficient in this type of bacteria, which suggests that they may not be receiving as much butyrate. Given butyrate’s many beneficial effects on blood sugar regulation, replenishing butyrate-producing bacteria can be a big step towards managing type 2 diabetes.
Similarly, Clostridium butyricum (WB-STR-0006) and Clostridium beijerinckii (WB-STR-0005) are two more butyrate-producing bacteria that are often reduced in people with type 2 diabetes. Many studies have focused on Clostridium butyricum and shown that replenishing this bacterial species can have clinical benefits for people with type 2 diabetes.
How can you increase these strains in your own microbiome?
Fortunately, there are steps you can take to increase the beneficial strains of bacteria in your gut microbiome. Boosting the beneficial bacteria in your gut can be done through a combination of increasing dietary fiber consumption through a largely plant based diet rich in various fruits and vegetables, forming routine exercise habits, and re-introducing key strains of bacteria through the use of probiotics.
The Right Nutrition
Bacteria strains that are believed to help protect us from type 2 diabetes can be nurtured and grown with a diet that includes fiber-rich foods. This includes foods such as:
- Beans and legumes (black beans, kidney beans, pintos, chickpeas, white beans, and lentils)
- Whole fruits and vegetables
- Nuts such as walnuts, almonds, and peanuts
- Whole grain pasta, cereal, and oats
- Flax seeds
Adding in prebiotics, such as inulin, also may help. Inulin is a type of complex carbohydrate that can promote beneficial bacteria in the gut.15 Foods rich with inulin include:
Adding these foods to your diet can help ensure that there is a consistent food source for the beneficial bacteria. Be mindful to speak with your healthcare provider about adding these foods to your current eating plan. If you have been on a diet devoid of dietary fiber, like the majority of people in the US who consume a standard American diet, it is important to add fiber slowly but consistently to your diet.
However, while the food source is important, it is also important to cultivate the gut microenvironment to be favorable for these bacteria.
Exercise and Stress Reduction
Exercise appears to play an important role in shaping the gut microbiome. People who exercise moderately but regularly tend to have more beneficial bacteria represented in their gut microbiome.
Exercise can be particularly helpful for people with prediabetes and type 2 diabetes for a number of reasons that go beyond the gut microbiome. It has been shown that regular exercise can help reduce blood A1C levels and lead to weight loss, both of which are associated with healthy blood sugar regulation. Similarly, studies suggest that taking steps to reduce stress is likely to help encourage the growth of beneficial bacteria and ultimately reduce blood sugar levels.
Both stress and exercise have been shown to have an influence on gut microbial composition and function, and on gut health. Numerous studies have shown that reducing stress and increasing exercise correlates with a healthy gut microenvironment and higher levels of beneficial bacteria.
The Right Probiotics
As mentioned earlier, the gut microbiome is a complex ecosystem that involves harsh competition between species. To help the species that protect us from type 2 diabetes to thrive, it’s important to give them a consistent food source (fiber in particular) and to make the environment as favorable to their growth and survival as possible. This is where pre and probiotics come in.
There are many probiotics in the market, each directed towards a specific set of conditions. With so many out there, it can be difficult to know what is the best probiotic supplement for people with type 2 diabetes. Generally speaking, you should look for one of the few probiotic products that is backed by high quality clinical evidence demonstrating efficacy in type 2 diabetes. This will likely include a combination of bacteria that help to increase butyrate production and reduce the leakiness of the gut. Some probiotics will also include a prebiotic like inulin as a starter food for the bacteria; this is to help the bacteria hit the ground running, so to speak.
When we think about health and disease, the invisible bacterial community residing deep within our gut is often overlooked. But the past decade has revealed just how important the microbiome is for our health and what important role changes in our microbiome play in many of our most common chronic diseases, including type II diabetes.17 It’s a rich ecosystem teaming with life; and, like all ecosystems, it needs to be cared for.
We can care for our microbiome by forming routine exercise habits, reducing stress where possible, and by adding fiber and probiotics to our diet. When we do these things, we favor the growth and survival of bacteria that help protect us from many different conditions, even type 2 diabetes.
- Gurung, Manoj et al. “Role of gut microbiota in type 2 diabetes pathophysiology.” EBioMedicine vol. 51 (2020): 102590. doi:10.1016/j.ebiom.2019.11.051
- Tai, Ningwen et al. “The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity.” Reviews in endocrine & metabolic disorders vol. 16,1 (2015): 55-65. doi:10.1007/s11154-015-9309-0
- Ortega, Miguel A et al. “Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications.” Nutrients vol. 12,9 2749. 9 Sep. 2020, doi:10.3390/nu12092749
- Liu, Hu et al. “Butyrate: A Double-Edged Sword for Health?.” Advances in nutrition (Bethesda, Md.) vol. 9,1 (2018): 21-29. doi:10.1093/advances/nmx009 https://pubmed.ncbi.nlm.nih.gov/29438462/
- Ojo, Omorogieva et al. “The Role of Dietary Fibre in Modulating Gut Microbiota Dysbiosis in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.” Nutrients vol. 12,11 3239. 23 Oct. 2020, doi:10.3390/nu12113239
- Madsen, Mette Simone Aae et al. “Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice.” Scientific reports vol. 9,1 15582. 30 Oct. 2019, doi:10.1038/s41598-019-52103-x
- Gérard, Céline, and Hubert Vidal. “Impact of Gut Microbiota on Host Glycemic Control.” Frontiers in endocrinology vol. 10 29. 30 Jan. 2019, doi:10.3389/fendo.2019.00029
- Boets, Eef et al. “Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study.” The Journal of physiology vol. 595,2 (2017): 541-555. doi:10.1113/JP272613
- Xu, Yu, et al. “Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems.” Frontiers in Microbiology, vol. 11, 2020, doi:10.3389/fmicb.2020.00219. /fmicb.2020.00219/full
- Bermon S;Petriz B;Kajėnienė A;Prestes J;Castell L;Franco OL; “The Microbiota: an Exercise Immunology Perspective.” Exercise Immunology Review, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/25825908/
- Cully, Megan. “Antibiotics Alter the Gut Microbiome and Host Health.” Nature News, Nature Publishing Group, 17 June 2019, www.nature.com/articles/d42859-019-00019-x.
- Karl, J Philip et al. “Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota.” Frontiers in microbiology vol. 9 2013. 11 Sep. 2018, doi:10.3389/fmicb.2018.02013
- Nagpal, Ravinder et al. “Gut microbiome and aging: Physiological and mechanistic insights.” Nutrition and healthy aging vol. 4,4 267-285. 15 Jun. 2018, doi:10.3233/NHA-170030
- Li, Yuanyuan, et al. “The Role of Microbiome in Insomnia, Circadian Disturbance and Depression.” Frontiers, Frontiers, 20 Nov. 2018, www.frontiersin.org/articles/10.3389/fpsyt.2018.00669/full
- “Inulin Dietary Fiber with Functional and Health Attributes-A Review.” Taylor & Francis, www.tandfonline.com/doi/abs/10.1080/87559121003590664
- Kashyap, Purna C. et al. “Genetically Dictated Change in Host Mucus Carbohydrate Landscape Exerts a Diet-Dependent Effect on the Gut Microbiota.” Proceedings of the National Academy of Sciences of the United States of America 110.42 (2013): 17059–17064. PMC.
- The Gut Immune Connection by Emeran Mayer, MD
Colleen Cutcliffe, PhD is the CEO and Co-Founder of Pendulum Therapeutics. Pendulum is a startup company based in San Francisco that uses biological and computational insights into the microbiome to develop interventions for a variety of health and disease conditions.