As these GEITP pages have often stated, any trait (phenotype) reflects contributions of: [a] genetics (differences in DNA sequence); [b] epigenetic factors (chromosomal events independent of DNA sequence. The four accepted subdivisions include: DNA methylation, RNA interference, histone modifications, and chromatin remodeling); [c] environmental effects (e.g., smoking, diet, lifestyle); [d] endogenous influences (e.g., kidney or cardiopulmonary disorders); and [e] each person’s microbiome. The topic today fits well with the theme of gene-environment interactions. One “signal” is dietary sugar and endogenous influences such as obesity. The genes that “respond to this signal” make the patient more susceptible to type-2 diabetes (T2D).
The fascinating aspect of this article [below] includes important advances in better understanding of our microbiome. Therefore, another “signal” represents metabolites generated by specific anaerobic bacterial species — which lead to a higher risk of T2D (the “response”); this is because these metabolites have been discovered to be underrepresented in the gut of T2D patients (having A1c levels of 6.5% or higher) and prediabetic patients (having A1c levels of 5.7% to 6.4%). This company’s particular preparation thus includes the oligosaccharide-consuming Akkermansia muciniphila and Bifidobacterium infantis, the butyrate producers Anaerobutyricum hallii, Clostridium beijerinckii, and Clostridium butyricum — along with the “prebiotic” dietary fiber inulin.
For those who have followed the explosion in our understanding of the gut microbiome, it wasn’t that long ago (perhaps 2005?) when we knew almost nothing about bacteria in our intestine (and elsewhere on the body) and what they do. Now we realize that, if one grinds up an entire mammal (or human) and isolates total DNA — ~92% of this DNA represents our bacteria (!!). Moreover, the “brain-gut-microbiome” represents an important axis of innumerable functions that can cause or influence changes in health, disease, and even our mood and behavior (all elicited by gut bacterial metabolites). To our knowledge, this probiotic preparation* (Pendulum Glucose Control) — containing gut bacterial strains that are deficient in people with pre-T2D or T2D — is the first example of Big Pharma utilizing knowledge gained by studying our gut microbiome, to (hopefully) improve (or prevent) clinically an undesirable and very serious disease. 😊😊
*Even though it is a rather expensive daily medication for the average patient ☹…
DwN
COMMENT: — there is a bit of a disconnect between your comments on fecal microbiota transplantation (FMT) and the Medscape article that GEITP had featured [pasted furthest below]. Many clinical centers are randomly trying FMT on virtually every human disorder — “to see if it works” (i.e., if it helps, or prevents, X-Y-Z). This is all well and good.
In contrast, this pharmaceutical firm took advantage of the discovery of the absence (or very low levels) of specific strains of anaerobic bacteria in patients with type-2 diabetes (T2D) or those showing signs of pre-T2D, compared with patients having no T2D or pre-T2D. The company then developed a preparation that includes [a] two oligosaccharide-consuming bacterial strains, [b] three butyrate-producing strains — combined with [c] the “prebiotic” dietary fiber inulin. Coming up with a specific commercial preparation … is wherein the creativity resides.
Imagine a fly on the wall 30 ft away, which you’d like to eliminate. 😊 The former approach is like a shotgun blast, hoping to hit the fly. The latter approach is like designing a laser gun to hit the fly specifically. 😊 The latter is therefore an example of “precision medicine.”
DwN
COMMENT: I agree that fecal microbiota transplantation (FMT) is amazing with its potential. To my knowledge, FMT has been most remarkably and reproducibly useful for treatment of persistent C. difficile infections. Here is the Cell Metabolism reference (and another in Gut and a newspiece) and here is the quote from the book where I first learned of this:
“Research is underway examining how certain probiotics might be able to reverse type-2 diabetes and the neurological challenges that can follow. At Harvard’s 2014 symposium on the microbiome, I was floored by the work of Dr. M. Nieuwdorp from the University of Amsterdam, who has done some incredible research related to obesity and type-2 diabetes. He has successfully improved the blood sugar mayhem found in type-2 diabetes in more than 250 people using fecal transplantation. He’s also used this procedure to improve insulin sensitivity.
These two achievements are virtually unheard of in traditional medicine. We have no medication available to reverse diabetes or significantly improve insulin sensitivity. Dr. Nieuwdorp had the room riveted, practically silenced, by his presentation. In this experiment, he transplanted fecal material from a healthy, lean, nondiabetic into a diabetic. What he did to control his experiment was quite clever: He simply transplanted the participants’ own microbiome back into their colons, so they didn’t know whether they were being “treated” or not. For those of us who see the far-reaching effects of diabetes in patients on a daily basis, outcomes like Dr. Nieuwdorp’s are a beacon of hope. […]”
Excerpt From: David Perlmutter. “Brain Maker: The Power of Gut Microbes to Heal and Protect Your Brain for Life.” iBooks.