|B2201561-Bifidobacterium_bifidum-SPL by tiendat40, on Flickr|
Above is a picture of a strain of Bifidobacterium bifidum, one of the "good guys" we want to increase using the GAPS protocol. I suspect gut bacteria may have a large effect on T2 diabetes for a few reasons: the observed fact that gastric bypass surgery has cured T2 diabetes and that a woman with treated with Clostridium difficile by a fecal transplant from her husband was cured of T2. But the thing that convinced me to try GAPS myself is new evidence that T2 is an autoimmune disorder.
evidence that T2 diabetes is an autoimmune disease
First in 2009, Winer et al found that immunosuppressant drugs reduced T1 cells in VAT (belly fat) and reversed insulin resistance for months, implying the immune system is involved in T2 diabetes:
Obesity and its associated metabolic syndromes represent a growing global challenge, yet mechanistic understanding of this pathology and current therapeutics are unsatisfactory. We discovered that CD4+ T lymphocytes, resident in visceral adipose tissue (VAT), control insulin resistance in mice with diet-induced obesity (DIO). Analyses of human tissue suggest that a similar process may also occur in humans. DIO VAT-associated T cells show severely biased T cell receptor Va repertoires, suggesting antigen-specific expansion. CD4+ T lymphocyte control of glucose homeostasis is compromised in DIO progression, when VAT accumulates pathogenic interferon-? (IFN-?)-secreting T helper type 1 (TH1) cells, overwhelming static numbers of TH2 (CD4+GATA-binding protein-3 (GATA-3)+) and regulatory forkhead box P3 (Foxp3)+ T cells. CD4+ (but not CD8+) T cell transfer into lymphocyte-free Rag1-null DIO mice reversed weight gain and insulin resistance, predominantly through TH2 cells. In obese WT and ob/ob (leptin-deficient) mice, brief treatment with CD3-specific antibody or its F(ab')2 fragment, reduces the predominance of TH1 cells over Foxp3+ cells, reversing insulin resistance for months, despite continuation of a high-fat diet. Our data suggest that the progression of obesity-associated metabolic abnormalities is under the pathophysiological control of CD4+ T cells. The eventual failure of this control, with expanding adiposity and pathogenic VAT T cells, can successfully be reversed by immunotherapy.
Then in April 2011, Winer & Winer et al published showing B cell involvement:
Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity-associated insulin resistance and glucose intolerance. Here we show a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B cells accumulate in VAT in diet-induced obese (DIO) mice, and DIO mice lacking B cells are protected from disease despite weight gain. B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies. Treatment with a B cell–depleting CD20 antibody attenuates disease, whereas transfer of IgG from DIO mice rapidly induces insulin resistance and glucose intolerance. Moreover, insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. These results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities for managing the disease.
The entire articles are available online for a fee; the abstracts and data diagrams are available free; see references.
explanation of research
These researchers noticed that the belly fat of T2 diabetics was inflamed. They hypothesized that as fat cells died, they were invoking an immune reaction.
The way immunity normally works is that some white blood cells (lymphocytes) recognize a protein as foreign (antigen). They "eat" it and then they stick the digested bits on their cell membranes where they can be "seen" by other cells. The type of lymphocytes that do this are called B cells, because they mature in the bone marrow.
T lymphocytes (called T because they mature in the thymus gland) come in several types. The first are helper T cells, which attach to the B cell and help it reproduce itself, and then produce soluble antibodies. Antibodies are proteins that "stick" to antigens.
So the antibodies float around in the blood, sticking to any of "their flavor" of antigen. The antibodies are a signal to another type of T cell, the cytotoxic (cell-killing) ones, that kill the cell with the antibody on it.
Actually, there's a lot more to immunity, but that's a simplified explanation for now.
In a perfect world, antibodies only mark out virally-infected and tumor cells, so only these get killed. In a less-perfect world, the immune system recognizes non-foreign proteins as antigens, thus attacking normal healthy cells; this is what we mean by an autoimmune disease. Type 1 diabetes, in which the beta cells of the pancreas are destroyed, is an autoimmune disorder; another common example is Hashimoto's in which the thyroid gland is attacked by the immune system.
People who need organ transplants are given drugs to suppress their immune systems so they won't attack the organ - these are called immunosuppressants.
So in the first study, they took a strain of mice that they knew they could give T2 easily with a particular diet and gave some of them an immunosuppressant drug, and found they had fewer T cells in their belly fat, and that insulin resistance was postponed for several months.
In the second study, they grew some mutant mice that couldn't make any B cells, so they couldn't make antibodies. They fed them the diabetes-causing diet, but they didn't get diabetes. Then they took antibodies from the blood of diabetic mice and injected them in the mice that couldn't make antibodies themselves, and they got diabetes.
These studies imply that diabetes is an autoimmune disorder. But most of us are more interested in human diabetes than mice diabetes.
But you can't test people this way, as it takes too long to breed them and they complain if you suppress their immune systems willy-nilly (being a lot more whiny than mice). So instead they took a bunch of equally fat guys, some with T2 and some without, and looked at their blood, and found these same antibodies in the diabetics but not in the nondiabetics.
The theory upon which Gut and Psychology Syndrome is based is that peptides (small protein chunks) from gluten and casein leak through the gut into the bloodstream, cross the blood-brain barrier, and act as opiates, effecting the cognition of the individual.
This theory may or may not be correct. However, Dr. Campbell-McBride has been very successful treating patients on the autism spectrum with the GAPS protocol. In the process of treating her patients and their families, she saw a decrease in autoimmune issues such as allergies and asthma.
Because the protocol directly works with the gut, many folks with GI diseases, such as colitis, Crohn's, IBS and celiac, have found relief with the protocol. And because it "heals and seals" the gut, it has relieved many folks of various autoimmune issues.
In the TF community, there have been many reports of people who achieved great success with myriad gut and autoimmune issues using this protocol. Thus my conclusion that it's worth a shot for T2 diabetes.
Winer, S.; Chan, Y.; Paltser, G.; Truong, D.; Tsui, H.; Bahrami, J.; Dorfman, R.; Wang, Y.; Zielenski, J.; Mastronardi, F.; Maezawa, Y.; Drucker, D.; Engleman, E.; Winer, D.; Dosch, H-M. Normalization of obesity-associated insulin resistance through immunotherapy. Nat. Med. [Online] 2009, 15, 921 - 929. http://www.nature.com/nm/journal/v15/n8/full/nm.2001.html (accessed Jul 9, 2012).
Winer, D. A.; Winer, S.; Shen, L.; Wasia, P. P.; Yantha, J.; Paltser, G.; Tsui, H.; Wu, P.; Davidson, M.; Alonso, M.N.; Leong H. X.; Glassford A.; Caimol, M.; Kenkel, J. A.; Tedder, T. F.; McLaughlin, T.; Miklos, D. B.; Dosch, H-M; Engleman, E.G. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. [Online] 2011, 17, 610–617. http://www.nature.com/nm/journal/v17/n5/abs/nm.2353.html (accessed Jul 9, 2012).
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