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Pop a squat

Posted in Uncategorized on April 21, 2012| 18 Comments »

I lied.

 

I said I was going to take a break from writing about bowels and microbiota (I was, I really was), but then my awesome chief resident (the head of my surgery team) distracted me with bowels again.  After I revealed my interest in evolutionary medicine (followed by a brief rant on the appendix, gut microbiota, and the general tenets of evolutionary medicine) he said “Cool- let’s see what kinds of patients I can find for you”.  He then assigned me a few patients with some thoughts of things I should look up and get back to the team on.  I was thrilled.  The patients were interesting and the things he suggested I look up were spot-on… He totally ‘gets it’.

 

Diverticula are out-pouches of the colon, and can either be “true” diverticula, consisting of all layers of the bowel wall, or “false” (AKA pseudodiverticula), where the thin layers of the bowel balloon out through gaps in the muscular layer.  Diverticula can occur on the right side of the colon (the part closest to the small intestine) but are much more common (at least in the Western world) on the left side, particularly in the sigmoid colon (the last bit of the colon before the rectum).  These are almost always “pseudodiverticula” though are generally referred to as “diverticula” and are the type I will discuss in this post.

 

Diverticula were once considered so rare that surgical textbooks from the early 1900s didn’t even mention them.  It is now thought to be one of the most common colonic conditions in the developed world, though the prevalence is difficult to determine as most cases are asymptomatic.  Current estimates, however, are that more than 40% of people in industrialized nations develop diverticula by the age of 60, and more than 60% develop them by the age of 80.  As I mentioned, diverticula are frequently asymptomatic, but we become aware of them when they become inflamed, infected, or abscessed, leading to a condition known as diverticulitis (interestingly, diverticula on the right are more prone to bleed, while the ones on the left are more likely to become infected).

 

The pathogenesis of diverticula is generally believed to be dependent on the intraluminal pressure of the colon, specifically increased pressure during defecation.  While straining to ‘perform’, the pressure in the colon greatly increases, especially in the areas closest to the rectum.  Exaggerated contractions with spasmodic bowel movements cause increases in bowel pressure that may lead to diverticula.  Conventional wisdom would have you believe that increased peristaltic activity is caused by our industrialized low-fiber diet, which leads to low-bulk stool, which cause our colon to work extra hard to expel their payload.  You might suspect, however, that I am a little skeptical of conventional wisdom (refreshingly, so is my chief resident!).

 

The thought process that led to a ‘fiber-deficiency’ model of diverticular disease is actually rather encouraging for those of us who appreciate an ancestral approach to health.  The argument was initially made by Burkitt and Painter [1] who in 1975 compared the stool transit time and volume of native Ugandans (a population virtually devoid of diverticula) with that of native Britons (importantly, while native Africans do not develop diverticula, those of African descent living in the developed world do).  Burkitt and Painter realized that Ugandans had much larger (450g/day vs. 110g/day) stools and a much shorter transit time (34 hours vs. 80 hours) than UK natives.  It was reasoned that these differences were caused by decreased fiber consumption in the developed world.

 

Alas, while this argument has gained substantial credence through years of reinforcement, the case for diverticula being a disease of a fiber deficiency fails to hold up.  In fact, a paper recently published in the Journal of Gastroenterology is just the most recent take down of the fiber-based model of disease [2].  This paper adds to the library of references that have failed to show a link between low-fiber diets and diverticula.  In fact, this paper actually suggests that the inverse is true, with those that consumed the most fiber having the highest incidence of diverticula.  This paper also took a look at other factors often implicated in diverticular disease, specifically infrequent bowel movements, high-fat diets, diets with a lot of red meat, and physical inactivity.  None of these factors were associated with diverticulosis (indeed, people with few bowel movements had fewer diverticula than those with many!).

 

So if a lack of fiber doesn’t cause diverticula, what does? In their 1975 paper, Burkitt and Painter focused on the fiber content of the native diet of Ugandans.  Their focus on diet, I fear, has led astray those who seek to prevent diverticular disease.  While it is true that native Ugandans ate an evolutionary-appropriate diet, they ALSO utilized evolutionary appropriate behavior… For lack of a more tactful explanation- they squat to defecate and only go when they feel the need!  Shocking, I know.

 

The hypothesis that diverticula could be prevented by squatting and urge-driven bowel habits was put forth in a 1988 paper (in one of my favorite journals, Medical Hypotheses), which pointed out that underdeveloped nations (which have an exceptionally low prevalence of left sided diverticular disease) utilize latrine pits.  They went on to point out that bowel emptying in a sitting position, as caused by a western toilet, requires multiple straining efforts, while bowel empting upon urge in a squatting position usually only requires one [3].  This suggestion has been followed up with a couple of recent studies that show that straining to defecate is greatest in the standing or lying position and minimized in the squatting position [4, 5].  Anatomically, this is explained by the change in the recto-anal angle, which becomes aligned in the squatting position and is obstructed as the flexion of the hips is decreased.

 

An interesting aside at this juncture is a quick look at the prevalence of diverticular disease in Japan.  As an Asian country, Japan used to have a higher prevalence of right-sided diverticular disease, with left-sided being fairly uncommon.  This trend, however, started to change with the westernization of Japan.  Following Burkitt and Painter, the increase in left sided diverticular disease has been attributed to a decrease in fiber in the westernized Japanese diet [6], but is the blame duly placed?  My brother has lived in Japan for many years and I’ve visited a number of times, and I’ve often been impressed by the spectrum of toilets available in Japan.  They range from the  ‘traditional’ Japanese squatting toilet (a ceramic latrine set in the ground) through to the modern toilet which is an amazing feat of engineering (perhaps you’ve seen one on TV somewhere- they come complete with jets that direct warm water and warm air at various body parts, play music to hide unwanted sound effects, and may, in fact, be able to tell you the answer to the ultimate question of life, the universe, and everything).  Is it fair to blame a lack of fiber on the increase in diverticular disease in Japan?  Or might it actually be due to a conversion from the traditional squatting toilets to westernized seated ones?

 

“Seated-stooling” has also been implicated in other conditions of the bowel.  There’s another Medical Hypotheses paper that names sitting as a mechanism underlying primary constipation [7], and another communication from the Israel Medical Journal describing a neat little trial conducted on patients with hemorrhoids [8].  This small trial, consisting of only 20 patients, showed interesting results.  Of the 20 patients, 17 had tried (with minimal success) conservative treatment for hemorrhoids, including the ‘all-curing’ high-fiber diet, as well as suppositories, salves, and laxative preparations.  The remaining 3 patients had undergone ligation for severe hemorroids.  Throughout the course of this study (conducted over 1 year) the patients were asked to defecate in a squatting position only and to defecate only in response to a strong urge (no straining to perform!).  The result of these interventions was alleviation of symptoms in most patients.  Alas, 2 of the 3 who had undergone ligation did not experience significant improvement, which may have been a result of fibrous tissue development at the site of ligation.

 

The conclusion of this last paper seems particularly fitting in consideration of the overlying evolutionary-based interests of this blog: “that a program may be needed to reacquaint man with his natural habits.”[8].  (No, you don’t need a pit latrine- there are little stools available designed to fit around toilets that allow you to squat over the pot! (Here’s an example, with the option to ‘build your own’)

 

 

1.            Painter, N.S. and D.P. Burkitt, Diverticular disease of the colon, a 20th century problem. Clin Gastroenterol, 1975. 4(1): p. 3-21.

2.            Peery, A.F., P.R. Barrett, D. Park, A.J. Rogers, J.A. Galanko, C.F. Martin, and R.S. Sandler, A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology, 2012. 142(2): p. 266-72 e1.

3.            Sikirov, B.A., Etiology and pathogenesis of diverticulosis coli: a new approach. Med Hypotheses, 1988. 26(1): p. 17-20.

4.            Sikirov, D., Comparison of straining during defecation in three positions: results and implications for human health. Dig Dis Sci, 2003. 48(7): p. 1201-5.

5.            Rao, S.S., R. Kavlock, and S. Rao, Influence of body position and stool characteristics on defecation in humans. Am J Gastroenterol, 2006. 101(12): p. 2790-6.

6.            Nakaji, S., K. Sugawara, D. Saito, Y. Yoshioka, D. MacAuley, T. Bradley, G. Kernohan, and D. Baxter, Trends in dietary fiber intake in Japan over the last century. Eur J Nutr, 2002. 41(5): p. 222-7.

7.            Sikirov, B.A., Primary constipation: an underlying mechanism. Med Hypotheses, 1989. 28(2): p. 71-3.

8.            Sikirov, B.A., Management of hemorrhoids: a new approach. Isr J Med Sci, 1987. 23(4): p. 284-6.

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For babies’ microbiota- breast is best

Posted in Uncategorized, tagged , on March 15, 2012|

‘Breast is best’ is the rallying cry of many who want to encourage mums to breastfeed their children, though some think the slogan should be banished. To those who wish to do away with the slogan, it’s not a matter of what is ‘best’ but a matter of ‘biologically normal’. I’ll admit to being rather nonplussed about slogans, but I am rather adamant that one should put trust in basic biology when possible.

 

Over the years, studies have shown correlations suggesting many benefits of breastfeeding, including increased IQ, decreased obesity, and a decrease in several pediatric ailments such as gastritis and ear infections in the offspring (I think those last two are particularly interesting). While these studies are interesting, they are just correlations, and I hate to put too much weight on correlative studies (though they can be fun to look at).

 

Biology is marvelously complex. As a result, studying it and then mimicking it is time consuming and tricky. I think breastfeeding is a wonderful example of a fascinating bit of biology that shows us how tricky it is to properly and fully study complex biology, and also shows us how humans have evolved to thrive on the ‘evolutionary norm’ (breastfeeding).

 

Breast milk is interesting stuff- though to be honest, some species have much more interesting milk than humans, with some species producing milk that changes in composition from day to day (and even different compositions from different nipples to feed different offspring!). While breast milk provides sustenance for an infant, it also helps develop the immune and metabolic systems of the offspring. The composition of breast milk can pass along information from mother to child, relaying information about the relative abundance or paucity of the environment in which the offspring will develop. This transfer of information, and the relative role of this communication in growth and development, is a fascinating area of research.

 

If people think about breast milk in the context of immunity, they generally think of the active transfer of antibodies from mother to child. The earliest milk produced by a mother, colostrum, is particularly rich in antibodies, and imparts great benefits to an infant. Even mothers that don’t wish to breastfeed extensively are encouraged to at least nurse in the early days of a neonate’s life so as to transfer these important antibodies. But is that it on the breast milk/immune system link?

 

In my last few posts I’ve touched on the importance of the gut in a number of immune mediated responses. The gut is actually rather rich with immune tissue, and fosters a number of bacteria (hopefully helpful and health-promoting ones) that help keep out nasty pathogenic invaders (and also helps keep the gut healthy in other ways, such as producing short chain fatty acids to nourish cells and producing Vitamin K). In my last few posts, I’ve talked about the appendix, and how it appears to have evolved as a safe house for our native microbiota in times of duress. But where do these bacteria come from?

 

Before birth, the intestinal tract of the fetus is thin and immature- lacking any significant lymphoid tissue. The intestine of a newborn develops substantial lymphoid tissue, which indicates the active bacterial colonization of the gut, altering its structure and function. There appear to be three phases of normal gut colonization in an infant starting with whatever flora are picked up during a normal vaginal delivery. The process of breast-feeding ushers in a second phase of colonization, with the third and final stage occurring at weaning. During colonization, it appears that infants generally inherit their mother’s microflora [1], and if all goes well- this is what will populate your appendix!

 

Any one with an eye to evolution might suspect that breast milk is exquisitely effective at producing healthy offspring- we’ve been making this stuff for hundreds of thousands of years… it is nuanced in ways we’ve yet to even think about. One thing we are starting to understand is that the composition of breast milk fosters a healthy microbiome in infants. In addition to the protein, fats, and carbohydrates that make up breast milk and nourish the child, there are a number of products present in breast milk that can’t be actively digested by the infant, but that are excellent fodder for a blossoming gut microbiome. These compounds are known as human milk oligosaccharides (HMOs- not the annoying health insurance type), and we’re nowhere close to identifying all the different types, though we know there are more than 100 different molecular structures. These molecules are resistant to gastric acid and aren’t absorbed or metabolized by the baby, and instead make it to the large intestine where they can be fermented by intestinal microflora. 

 

The gut microbiome of infants that are breast fed is quite a bit different from that of formula-fed babies. A number of studies have looked into this, and I don’t want to go into details of different studies, but there appear to be significant differences in the type and number of bacteria in the gut of these populations. Depending on the study, findings showed babies that had been breast-fed tended to have the same amount or more ‘good’ bacteria (Lactobacillus sp. and Bifidobacterium sp.) and less ‘bad’ bacteria (E. coli and C. diff (remember that guy from my last post?)). Breastfeeding probably helps set the microbiome up for success in a number of ways, including the direct transfer of bacteria from mother to child and also the transfer of maternally produced prebiotics that encourage appropriate bacterial growth. There’s also evidence that there is a significant difference in the pH of the large intestines of breast-fed vs formula-fed infants (an acidic pH in breast-fed infants vs a fairly neutral pH in those fed formula). I’m not sure how much of this is a result of appropriate bacterial growth, and how much that acidic pH then encourages more appropriate bacterial growth, but it’s fun to think about (it’s probably a nice little positive feedback loop).

 

Setting the neonatal microbiome up for success is just one of the many roles that breast milk has evolved to excel at. As mentioned above, breast milk is incredibly complex, and we are only starting to understand the many ways in which is sets an infant up to thrive (and not just survive). In the ideal world, all mothers would breast feed exclusively for 6 months, and then continue to breast feed while foods are introduced, but unfortunately, reality is not this easy. For some, formula is a necessity.  So how can we take what we know about breast milk and the infant microbiome and put this into practice?

 

In addition to the digestible micronutrients that are important for the proper growth of an infant, breast milk contains a vast array of non-digestible (but fermentable!) oligosaccharides that promote the development of a robust commensal microbiome. Knowing this, it seems appropriate to supplement formula with prebiotics that might equally foster the growth of appropriate microflora. There are a number of well-known prebiotics (perhaps the best known being inulin), but as we have yet to identify all the complex molecules in breast milk, we are unlikely to recreate the full spectrum of prebiotics offered by the ‘evolutionarily appropriate’ diet of an infant. Nonetheless, it appears that formula fortified (gosh I hate that word- if something needs to be fortified, I tend to think there’s a better, naturally more nutritious, option you should be consuming instead) with prebiotics might improve the gut microbiome in comparison to that of a regular formula-fed baby. A number of researcher groups have studied the effects of supplementation, with mixed results. Some have found positive effects of supplementation [2] (I’ll admit I’ve just read the abstract as I can’t read Chinese!) and some showing no difference [3]. This is not surprising, considering the complex nature of maternally produced prebiotics, but it does suggest that this is an avenue of investigation that should be further explored.

 

We are a long way off from making a formula that adequately and completely replaces breast milk. Like the gut microbiome (and growing infant!) that it nourishes, breast milk is extraordinarily complex, and we are only just exploring the tip of the iceberg of this massive subject. Nonetheless, realizing that breast milk helps promote a healthy microbiome (that you will hopefully keep for life!), which in turn helps develop a robust and appropriately directed immune system, should encourage researchers to further pursue this avenue of exploration. The more we learn about modern diseases, the more it appears that the integrity of the gut, and the functionality of the associated immune tissue, should be a central point of exploration for understanding disease.

 

1.            Kulagina, E.V., A.N. Shkoporov, L.I. Kafarskaia, E.V. Khokhlova, N.N. Volodin, E.E. Donskikh, O.V. Korshunova, and B.A. Efimov, Molecular genetic study of species and strain variability in bifidobacteria population in intestinal microflora of breast-fed infants and their mothers. Bull Exp Biol Med, 2010. 150(1): p. 61-4.

2.            Cai, J.W., Y.D. Lu, and X.M. Ben, [Effects of infant formula containing galacto-oligosaccharides on the intestinal microflora in infants]. Zhongguo Dang Dai Er Ke Za Zhi, 2008. 10(5): p. 629-32.

3.            Xia, Q., T. Williams, D. Hustead, P. Price, M. Morrison, and Z. Yu, Quantitative Analysis of Intestinal Bacterial Populations From Term Infants Fed Formula Supplemented With Fructo-Oligosaccharides. J Pediatr Gastroenterol Nutr, 2012.

 

 

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