Saturday, June 9, 2012

Gut Microbiota and PCOS

Every few months I scour pubmed.org for the latest research on PCOS. Polycystic Ovarian Syndrome is an endocrine disorder that affects 5-10% of women.  It can lead to infertility and Type II diabetes, and manifests as amenorrhea, insulin resistance, obesity, acne, hirsutism, a chronic inflammatory state, or a combination of these symptoms.  I will write at length later about how I was diagnosed and how I've significantly alleviated the symptoms since then, but today - new research.

Why do I scour pubmed? Two reasons:

1) to scare myself into taking action to heal myself. As a "lean PCOSer," it is far too easy to forget that you have an issue to resolve when to everyone else, you look perfectly healthy.

2) to glean new insights into etiology of the syndrome. Exercise for the mind, and potential practical applications.

I was definitely motivated to do more research today (aka scared shitless) after spotting a paper that found that people with PCOS are more likely to have children who score higher on the autistic spectrum (1). But to balance out those wonderful news, I came across a very exciting paper, perhaps the most exciting paper I've ever read on PCOS.

Why this paper made my year 

I've always thought that the etiology of PCOS had to do with a problem with gut flora, and I've wanted for years to do the GAPS diet to remedy it, but it was always an "inconvenient time" to start a dramatic diet. Experimentation with my own diet showed me there was profound change in the intensity of PCOS symptoms with changes in diet, and having worked in a microbiology lab, I assumed a large part of the change was due to changes in the colonic bacterial community.  Not to mention that there was a paper that found that women with PCOS had a decreased level of bacteria that convert a precursor to D-chiro-inositol, and that supplementation with DCI releaved some PCOS symptoms.  Though the sample size was small (15 people), sales of DCI shot up, but it seemed like too simplistic of an explanation to me. A miraculous supplement that will cure you of this complex syndrome? Probably not. But a microbial role in the syndrome? Very likely.

In the meantime, I recognized that many of my grandparents' ills were a direct result of years of antibiotic use (and abuse), and a diet filled with foods that frankly discouraged beneficial bacteria to ever consider colonizing their inhospitable colons. Then, in 2011, a good friend of mine was diagnosed with Ulcerative Colitis, an inflammatory condition of the colon linked with bacterial dysbiosis. Together we plunged into researching the best way to mitigate it.  We knew nothing about ways of treating it aside from the surgical removal of a portion of the colon (casually recommended by the Kaiser website) or a lifetime of anti-inflammatory drugs.  There was a deep uncertainty in the solution, but an equally deep conviction that there had to be a better way.  It was the most intellectually stimulating time, but also the most fulfilling research I've done to date. That was when we discovered the Specific Carbohydrate Diet and the GAPS diet, both concerned with reestablishing the microbial population of the gut. The histories of both diets are equal parts inspirational and fascinating, but I'll save that for a different post. The point is, the benefits of minding your gut microbiota are not trivial, and this has been known for some time.

So imagine my glee when my two main interests, gut health and PCOS came together in this paper: Dysbiosis of Gut Microbiota (DOGMA) - A novel theory for the development of Polycystic Ovarian Syndrome (2). 

From their abstract:
This novel paradigm in PCOS aetiology suggests that disturbances in bowel bacterial flora (“Dysbiosis of Gut Microbiota”) brought about by a poor diet creates an increase in gut mucosal permeability, with a resultant increase in the passage of lipopolysaccaride (LPS) from Gram negative colonic bacteria into the systemic circulation. The resultant activation of the immune system interferes with insulin receptor function, driving up serum insulin levels, which in turn increases the ovaries production of androgens and interferes with normal follicle development. 
 They essentially report that Leaky Gut Syndrome, a syndrome widely recognized in alternative practitioner circles, but not so much in traditional medicine, is the primary problem in PCOS.

The diet they implicate in the etiology is a high saturated fat/low fiber one. While I have qualms with a diet high in "saturated fat" being labeled a "poor diet" (the evidence doesn't stack up. Check out the work of Chris Masterjohn for more info), low fiber, and especially low vegetable-derived fiber is definitely problematic. 

The paper takes you through the step-by-step etiology of the disease, starting with disturbed colonic microbial balance and ending in hormonal disregulation. I can't recommend the read enough for anyone with PCOS. 

A fascinating idea  brought up in the paper (but not a cornerstone of their argument, in case you're unconvinced) was that increased visceral fat may be a direct result of its proximity to the gut:
As visceral adipose tissue is located close to the gastrointestinal tract, an impaired gut barrier function may expose this fat depot to various environmental agents, in particular bacterial antigens and immune factors. This in turn may stimulate, inter alia, adipogenesis. For example, localized lipopolysaccharide stimulation induces adipocyte hyperplasia in rats (3)
Another cool idea discussed was the connection between gut microbiota and insulin sensitivity. Gram-negative bacteria such as E. coli have molecules embedded in the outer membrane called Lipopolysaccharide, or LPS for short.  Since humans co-evolved with bacteria, one of the ways the human immune system has learned to recognize the presence of infection is through detecting LPS should it ever encounter it by mounting a strong immune response.  If this LPS enters the bloodstream, say through a permeable intestinal barrier (or  more colloquially, "leaky gut"), the body takes this as a red flag and wages an immune response - because hey, you may have bacteria in your blood - no bueno! For example, if you inject LPS into mice, their glucose sensitivity is compromised and they become more insulin resistant.  Conversely, increasing the "good" population of bacteria in the colon at the expense of the "bad" leads to improved insulin sensitivity.  From a separate British study that gave pregnant mothers probiotics:
The present study demonstrated that improved blood glucose control can be achieved by dietary counselling with probiotics even in a normoglycaemic population and thus may provide potential novel means for the prophylactic and therapeutic management of glucose disorders.
 Amen! 

To begin to remedy this problem, the authors suggest supplementation with the prebiotics inulin and FOS (Fructo-oligosaccharides), and the probiotics Lactobacillus rhamnosus GG, Lactobacillus gasseri, and Bifidobacterium lactic.  These probiotics are associated with weight loss.  It would be interesting to read about which other probiotics Western and non-Western physicians recommend, and to read more about what holistic medical systems like Ayurveda and Traditional Chinese Medicine recommend for improving intestinal health.  Intestinal health is central to wellbeing in both healing traditions. 




References

1) Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study.Clin Endocrinol (Oxf). 2012 May 21. doi: 10.1111/j.1365-2265.2012.04443.x.

2) Dysbiosis of Gut Microbiota (DOGMA) - A novel theory for the development of Polycystic Ovarian Syndrome.Medical hypotheses (2012)  volume: 79  issue:  page: 104-12

3) Pond CM. Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 2005;73:17–30.

4) R. Luoto, K. Laitinen, M. Nermes, E. Isolauri. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr, 103 (12) (2010), pp. 1792–1799

Sunday, February 12, 2012

Language barriers

Over the last year I've come to the conclusion that the only way to really help the grandparents in any lasting way is to go through the GAPS diet with them. Both have had extensive courses of antibiotics in the past and though they are rather resilient and eat only home cooked food, there are still signs that their digestion is not functioning optimally.  As Hippocrates said, "all disease begins in the gut," so that is what I'm targeting.

The first step in instituting this diet at home is simply explaining it and convincing the fam that it is necessary. Over the last few years, I've at least instilled some ideas about the value of organic food and the dangers of too much sugar, but this is an overhaul on a much bigger scale. One of the biggest challenges is that there are extremely few resources that explain the role of bacteria in gut and overall health in Russian. I've translated certain articles on Google Translate, which is a godsend, but some of them are awkward/hard to read, or simply too technical.

One article in Russian that gives a good overview is Вновь открытый орган, translated as "An Organ Rediscovered," which refers to the gut, or perhaps the human microbiome, which is gaining organ status in the literature recently.  The website I got it from, miloserdie.ru, is some sort of Orthodox Christian non-profit and has tabs that lead to articles on/for alcoholics, homeless people, orphans, and, the tab I got my article from - "the sick, the invalids, and the elderly." My grandma got a kick out of that subtitle. What's cool about the article is that it makes direct mention of the GAPS diet and its creator, Dr. Natasha Campbell-McBride. I've also printed out a stack of 30+ pages from the Russian-language version of the full GAPS diet. One factor that works in favor of them adopting this therapeutic diet is that it's very close to standard recommendations any Russian will give you, diet wise, if you're having upset stomach: eat more boiled, lightly cooked foods, drink tea, etc. Here's to hoping that with some interesting background info and some convincing, we could give this a shot.

Wednesday, September 7, 2011

Intro

Welcome! This is the inaugural blog post, appropriately written on Caltrain, on my useless blackberry, painstakingly pressed out, one pupil-sized keyboard button at a time.  So let's keep this short: my intention for this blog is to articulate / organize all of the health-related bits that float around in my head and to keep track of my efforts to optimize my family's health.

I can write endlessly about nutrition and health - the stimulation and inspiration I get from researching it, not to mention the physical benefits that I get out of actually eating well, but it all sounds too sappy and idealistic written out. Therefore, I will try to keep my enthusiasm to a level-headed, "scientific" medium setting, and my family will continue to bear the brunt of my occasional outbursts of nutrition-related mania... for now.