Diabetes and Gut Flora

There have been a large number of research papers of late dealing with the relationship between disease and the flora of the gut. There was a recent study from the University of Copenhagen’s Department of Biology and Novo Nordisk Foundation Center for Basic Metabolic Research which found that that people who have diabetes type 2 also have a unique gut bacteria profile. This may be helpful in early diagnosis of type 2 diabetes. It could also offer a therapeutic approach to treatment and it may also be a causal factor in the disease and it bears discussion.

Some Background

At birth the gut of a neonate is sterile, but bacterial seeding starts immediately after birth. Vaginally born infants will establish both maternal vaginal and environmental bacteria. Those born via a caesarean procedure will have predominantly more environmental bacteria. The maternal healthy vagina contains mostly Lactobacillus species. Bifidobacteria and other components of the normal human gut flora are obtained through environmental contact with soil and other terrain such as Aunt Kathy’s neck or fingers. This is actually the basis for an infant’s tendency to put everything in their mouth. It is not to be considered a negative action as it has evolved to be a trait necessary for survival as opposed to not receiving the maternal gut flora foundation of lactobacillus from vaginal delivery. It is estimated that there are up to 1.5kg of bacteria in the developed human gut which maintain a very delicate equilibrium.

http://www.sciencedaily.com/releases/2012/09/120926133111.htm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393882/

Many of theBacteria found in the gut cannot be studied by culture based methodologies. Newer methods used include the “gold standard” metagenomics a method by which the microbial genomes found in an environmental sample are studied to determine divisions (phylum) and species. This Study is called a metagenome-wide association study (MGWAS) and it allows one to study both mucosal and fecal samples to determine what divisions of bacteria are present. Deep gut microbial DNA was sampled from 345 Chinese individuals resulting in the identification of 60,000 type-2 diabetes markers to be used in the study

The divisions found in the intestines were:

• •Bacteroidetes
• •Fusobacteria
• •Firmicutes
• •Proteobacteria
• •Verrucomicrobia
• •Actinobacteria

Approximately 90% of the gut flora is comprised of two divisions, the Bateroidetes and Firmicutes while the remaining divisions account for the remaining 10%. Lactobacillus acidophilus is in the Firmicutes division and Bifidobacteria is in the Actinobacteria division.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393882/table/T1/?report=previmg

what did the study say?

The study showed that test subjects with type 2 diabetes suffered from gut dysbiosis, A decrease in the butyrate producing bacteria. This is significant because butyrate is the preferred source of energy, repair and maintaining health of colonic epithelia in the human digestive system. In the colon the predominant butyrate producing bacteria are the Clostridium coccoides and the Eubacterium rectale group. (1)

The study also found a rise in the number of opportunistic gut pathogens. There was also found to an enrichment of sulphate reduction which is important because sulphate selectively inhibits butyrate oxidation which is a hall mark of conditions such a ulcerative colitis. Increased oxidative stress resistance was also noted which implies that there is increased epithelial damage occurring. (2)

So what does this mean?

This is an engaging study that is part of a wider body of research being done on the gut flora and how it relates to the overall health of humans. Of course  many news editors will read the research and quickly make the leap that we can cure diabetes type 2 by treating the gut flora, but that remains to be seen. What we do know is that people who have diabetes type 2 are under a tremendous amount of metabolic stress due to their body’s inability to properly place the glucose in their blood stream into the cells of the body. Diabetes type 2 is characterized by damage to the glucose cellular transport systems. In areas of the body that do not have these glucose transport systems such as the nerves, the eyes and the brain you can see other forms of metabolic stress such as fructose-induced pressure in the eyes or AGE (advanced glycation end products) that can result sugars capping proteins rendering them useless and accounting for peripheral neuropathy, cataracts and blood vessel damage.(3) Brain function can also be affected.

The study pointed out that there is damage to the intestinal wall which means that higher molecular weight proteins can cross the intestinal wall and trigger white blood cells to release their inflammatory cascade resulting in increased inflammation.(4)Insulin resistance is associated with low-grade chronic systemic inflammation.(12) Much of this inflammation is due to the fact that approximately half of the body”s Lymphoid tissue is in the gut as the GALT tissue. If you combine this with bacterial endotoxins released as a result of intestinal dysbiosis plus the increased blood glucose levels you can see how the gut flora play a role in either increasing or decreasing the damage that can result from diabetes type 2.

So what does this mean for practicing clinicians?

In the future there will probably be a commercially available metagenomics test available. Checking in with various national labs revealed that is presently no such test available.  In the meantime clinicians can advise patients on dietary and supplement therapies which have already been shown to improve colonic health and gut flora.

Prebiotics

Prebiotics are non-digestible oligosaccharides that can act as fertilizers of beneficial colonic microbiota such as the highly beneficial bifidobacteria and lactobacillus(5)

Bifidobacteria have been shown to decrease colonic inflammation by a factor as high as 10 times more than other microbiota in the intestine(6) and will be talked about more later in this article. Prebiotics such as fructoligosaccharides are commercially available and can be used to modulate the growth of beneficial bacteria. Fructoligosaccharides (FOS), oligofructose and inulin are all inulin based prebiotics which were found to be Bifidogenic. (8) Inulin has also been used in commercial foods. One product available in the U.S. is a semolina pasta with inulin added called Dreamfields. Pasta with inulin has been shown in studies to improve cholesterol ratios, triglycerides and fasting glucose levels. (7) The use of prebiotics produces fast results, but it should be noted that these positive benefits can disappear in as little as 1 week when one stops taking the prebiotic.(9)

Prebiotics have also been shown to be effective in protecting against weight gain and even more significant is the resulting increase in the bifidobacteria resulted in less endotoxemia as was noted earlier.(10)(11)

Probiotics

There are so many species of probiotic bacteria out there that I could write a book on this topic alone, but being a clinician I will concentrate on the two major commercially available forms to point out their function and differences. The Lactobacillus rhamnosus species has been commercially available for many years and is the most commonly known and used probiotic. The major effect it seems to exert in the gut is the lowering of post prandial blood glucose levels(13). Lactobacillus delbrueckii supplementation also had a positive effect on fasting blood glucose levels (13) In studies it was pointed out that heat treated Lactobacillus did not have the effects that viable live bacteria did which  negates the value of food products which have their cultures added before they have been pasteurized. Another problem with food sources is that the number of colony forming units (CFUs) of bacteria drops over time so what may be in a yogurt when it leaves the factory may not be in it when you buy it.

Bifidobacteria has become popular over past 5years and with good reason because Bifidobacteria have been shown to reduce inflammation at the gut wall better than many other species of bacteria(3,4,6,11). Different strains of bifidobacteria were shown to inhibit LPS induced NF-KappaB which is a nuclear factor involved in chronic intestinal inflammation. (17) For the prevention of metabolic syndrome and to reduce the risk of diabetes supplementation with the beneficial forms of probiotics has evidence backing.

What about the butyrate producing bacteria?

Eubacteurium rectale can be influenced by diet and lifestyle choices. For example, a study found that eating almonds increased colonic populations of Eubacterium. (14)

Another study showed that NSAID usage in the elderly resulted in a decrease of this butyrate forming bacteria.(15) Bifidobacteria supplementation also increased Eubacterium rectale populations(16)

Discussion

When one first reads the headlines of news articles about research like this the mind always projects to the cause/effect model. The means we read the headlines and think “can bacteria directly cause diabetes?” and the answer is most likely no. Can your gut flora play a role in the development of diabetes type 2 and the answer is yes. The progression of ideas presented in this article goes like this:

The neonatal experience is determines the gut flora first, then dietary lifestyle choices influence which bacteria will proliferate and which will retreat in population. If your lifestyle choices leads to dysbiosis (soft drinks, a carbohydrate-based diet with little fiber, excessive use of pharmacological drugs) then there is a risk of increased inflammation which when combined with dietary high blood glucose levels can accelerate damage to both glucose regulated and non-regulated tissue which can lead to diabetes type 2 and various other medical problems. I think this same progression is also at the bottom of the increased rise in inner city pediatric asthma, general arthritis, allergies, heart disease and autoimmune conditions to mention a few. It is interesting in that hundreds of years ago the Chinese medical doctors knew that the basis of all disease could be found in the Spleen organ which in Chinese medicine was the pyloric valve, the bile, and the top of the small intestine. What they were describing was in essence the digestive function. They also attached a mental emotional component to a digestive disorder which has been researched separately as GALT (Gut Associated Lymphoid Tissue) and Interleukin 6 expression. The Chinese medical solution to dysbiosis was to eat cooked and not raw food, increase consumption of aromatic herbs such as ginger, fennel and cinnamon, and take herbal supplementation concentrating on herbs which will harmonize the digestion. The Chinese new hundreds of years before Pasteur and Bechamp that it is the terrain and not the bug that causes disease. What about bacteria affecting the genetics of the body to promote disease? Can it be like for other diseases which have a genetic component that increased inflammation causes so much tissue damage that repair and regeneration are accelerated to the point where there is a greater chance of genetic expression of a disease? In diabetes type 2 could that be a genetic predisposition towards inflammation, poor glucose metabolism or impaired metabolism?

What is known is that as clinicians there are definite steps we can take to help improve our patients quality of life while reducing the risk factors for developing type 2 diabetes. Theses steps embody a protocol to improve gut health through dietary changes, supplementation and pharmacological management. Hopefully in the near future a commercially available metagenomics test for predicting diabetes type 2 risk may become available.