A new study by an international team of scientists from Germany and the US (Endesfelder. 2016 | click here to read the study) appears to finally provide a mechanistic explanation for the previously postulated and epidemiologically observed link between a messed up gastrointestinal microbiome and the development of anti-islet cell autoimmunity (Brown. 2011; Giongo. 2011), i.e. the self-destruction of your pancreas.
Here's what the scientists did
Even though it is long-standing knowledge that "the development of anti-islet cell autoimmunity precedes clinical type 1 diabetes" and that the first signs of this rapidly accelerating process occur "very early in life," (Endesfelder. 2016) a mechanism to explain between the beginning self-destruction of the pancreas and the composition of the gut microbiome has yet been absent. To elucidate this mechanism, Endesfelder et al. developed a new approach to the analysis of the microbiome on an aggregation level between a single microbial taxon and classical ecological measures – and that not just for one type of bacteria, but for the whole microbial population.
If you think of the bacterial community in your gut as an ethnically diverse community, what the scientists did is tantamount to trying to identify, let's say the factors of economic success based on ethnicity and a whole host of co-variates including the ethnic diversity of the community, the local distribution of the ethnic groups, which ethnic groups cohabitate and interact, interactions within ethnic groups, etc. The result of this analysis would be a complex, but enlightening network (see Figure 1), based on which you can say much more about the link between ethnicity and economic success than based on a simple one-variable correlate analysis – no matter how many adjustments you make.
Based on the results of their network analysis, the scientists successfully identified three distinct sets of characteristic functional microbial communities. Of the three microbial communities (G31, G32, G33 in Figure 2) Endesfelder et al. identified, two showed no association with early antibody development, while the third, G33 in Figure 2, was associated with a significantly increased risk for early autoantibody development (note: this means they could but don't necessarily have to become type I diabetics, in fact, 1% of the healthy population carries the characteristic antibodies IA-2, GAD65, or insulin | Notkins. 2001 | illustration).
In this third group of children, the scientists observed an abundance of Bacteroides, a species of gram-negative bacteria, that was not present in the other two subgroups with low Bacteroides and increased Akkermansia abundances. This abnormality is highly problematic, because gram negative bacteria can cause various types of infections (NIH. 2012); and a correlative link to diabetes (type I and type II, by the way) has been observed in previous studies, too (Larsen. 2010).
What is triggering the autoimmune disease?
While further research will be necessary to satisfactorily answer what exactly it is that triggers the development of autoimmune antibodies, the study at hand points to at least two potential risk factors:
- the early introduction of a non-(mother's)milk diet – Evidence for a potentially causative link between the early introduction of non-milk foods to the diet and the development of T1DM is abundant. Kimpimäki, et al. (2001), for example, observed a significant increase in progressive beta-cell autoimmunity in response to (too) short-term breastmilk breastfeeding.
Other studies point to the early introduction (before 3 months) of specific food groups, with the most prominent example being gluten, which was associated with a 24-fold increase of the subjects' risk for islet autoantibodies in the BABYDIAB Cohort (Ziegler. 2003).
Whether and to which extent these effects are ultimately mediated by an immune reaction to the specific foods, and/or subsequent changes in the gut microbiome is yet still a topic of on-going research.
- a reduced production of butyrate via co-fermentation – The production of butyrate, a short-chain fatty acid and one of the predominant ketones in the human bodies, has been linked to the development of the development of autoimmune (=type I) diabetes, before (Davis-Richardson. 2015). As the primary energy source of the cells of your gut lining, butyrate does not just feed your intestinal epithelial cells, it will also increase their production of protective mucus and thus keep your gut from "leaking".
Without the protective mucus layer and a decreasing viability of the intestinal epithelial cells, larger molecules such as the pro-inflammatory lipopolysaccharides (LPS) from the cell walls of the already abundant Bacteriodes in the children in group three may penetrate the epithelial barrier (leaky gut hypothesis), promote local and systemic inflammation and eventually trigger immune reactions that result in severe damage to the pancreas.
Even though this appears to be the most convincing hypothesis there are alternative explanations, for example that "butyrate might also directly modulate immune function, in particular inflammation" (Endesfelder. 2016 or that the Bacteriodes, themselves, may have the ability to "trigger immune signals of the host in order to defend their ecological niche" (ibid.).
It remains to be seen, which of the previously discussed mechanisms contribute (most) to the development of auto-immune diabetes in children.
In view of results from animal studies which have linked the consumption of a gluten-containing diet to the same, significant decreases in the abundance of Akkermansia bacteria Endesfelder et al. observed in the auto-immune children in the study at hand (Marietta. 2013), it is if fact well possible that the early introduction of certain non-milk foods and the reduced production of butyrate via co-fermentation are intrinsically linked, with the former triggering the latter and thus, eventually, the development of type I diabetes.
What can you do to protect your children and yourself?
While it may not be the norm, it is possible to develop type I diabetes at any point in your life (usually as the end point of progressing latent auto-immune diabetes | see Stenström. 2005). Against that background means to promote the prevalence of butyrate producing bacteria and or the production of butyrate, in general, could protect infants, children and adults from seguing into type I diabetes. This is why I decided to close this article with a list of scientifically proven ways to boost your butyrate production:
- eat more foods that contain fiber, resistant starches and other prebiotics and eat them frequently – Consuming more fiber and resistant starch will promote the production of butyrate in your colon; ex-amples of such foods are oats, artichoke, chicory, bananas, onions, garlic, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, kale, etc.; to consume these foods frequently is im-portant, because the production of butyrate in the colon will decline when there's no supply of prebi-otic fiber (Knudsen. 2003)
- avoid antibiotics – Even though data is available only for children and the 16% increased risk of T1DM in children Hviid et al. (2009) observed in a nationwide study in Denmark was not significant, there's little doubt that the repeated use of antibiotics can trigger similar microbial imbalances as they have been observed in the study at hand. If you or your children have to use antibiotics, it would thus make sense to use probiotics and prebiotics to restore your weakened intestinal microbiome during and afterwards.
- don't obsess about hygiene – In spite of the fact that the validity of the "hygiene hypothesis" is still de-bated, no one debates the scientific evidence that links our obsession with sanitizers all sorts of auto-immune diseases, including, but not restricted to autoimmune diabetes (Okada. 2010).
- reduce your intake of high-fat foods and processed carbohydrate – Both high fat and highly processed high carbohydrate diets have been linked to reductions in intestinal butyrate production (irrespective of increasing systemic butyrate levels during fasting or in ketosis, which are a result of direct ketogenesis, not the formation of ketones in the gut). Supplementation of prebiotics, on the other hand, has been shown to counter some of the negative downstream effects of high fat diets (Gao. 2009).
- consume fermented = probiotic foods and or probiotic supplements – Probiotics, such as the lactobacil-li in yogurt have been shown to prevent the onset of autoimmune diabetes in rodent studies (Matsuza-ki. 1997); in view of the unclear link between dairy consumption and T1DM in infants, yogurt may yet not be the best choice for very young children (not: the evidence here is highly conflicting with selected studies actually showing a reduced risk of T1DM in children who are introduced to dairy, early).
- reduce your gluten exposure – In as much as I personally hate the "war on gluten", I cannot negate that, when it comes to autoimmune diseases, there's little doubt that gluten has the potential to trigger an already existing disposition for T1DM and other autoimmune diseases – specifically in early childhood (79% of children with T1DM develop full-blown celiac disease within <5 years of diagnosis | Pham-Short. 2015)
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