soluble fiber, the microbiome, and asthma

an article and editorial in Nature Medicine looked at dietary soluble fiber, changes in the gut flora (microbiome) and allergic airway disease. there have been articles suggesting that increased dietary fiber (esp soluble fiber) is linked to decreased risk of inflammatory diseases, esp in the gut. there are also some data finding associations between the higher incidence of asthma in those eating western diets and lower incidence on mediterranean diets. one potential explanation has been that gut microbes convert dietary fiber into short-chain fatty acids (SCFAs), which decrease inflammatory pathways in macrophages and dendritic cells, promote development of regulator T cells and maintain intestinal epithelial health.  for a detailed overview, see the editorial: asthma microbiome editorial nature medicine 2014 in the dropbox, or doi:10.1038/nm.3472.

in the current study (see asthma microbiome nature medicine 2014 in the dropbox, or doi:10.1038/nm.3444), researchers show how intake of high amounts of dietary fiber regulates the immune system in the lungs, decreasing the effect of  T helper type 2 cells allergy mediators, leading to lower allergic airway inflammation. (ie, dietary changes lead to immunologic changes in the lung). they had 2 different approaches to see if high soluble fiber diet could modulate airway inflammation. first, they fed mice a regular fiber diet vs low fiber diet, then exposed them to house dust mites, finding that the mice on the low fiber diet had elevated airway eosinophils, interleukins 4,5,13,and 17A, total IgE, dust mite specific IgG antibodies, mucous production and airway hyperreactivity. in a complementary experiment, they increased the fiber content of the food, with one group of mice fed high soluble fiber (30% pectin) and the control group given bulking fiber (30% cellulose). [in mice and men (humans....) pectin (but not cellulose) is fermented into SCFAs.] the high soluble fiber diet led to lower levels of allergic inflammation, decreased IgE, eosinophils and the above interleukins, and improved airway resistance. they also looked at the bacterial diversity of the GI tract, finding that it was increased in the high soluble fiber diet and decreased by the low-fiber diet -- supporting the relationship between diet, changes in the microbiome, and changes in physiology leading to differences in allergic response (presumably mediated through SCFAs).  for example clostridial species IV and XIAa, major producers of SCFAs, disappeared from mice on the low-fiber diet. there were also changes in the microbiome in the lung, though less impressive than in the gut. mice on the low-soluble fiber diet were then injected with propionate (an SCFA whose level was decreased in the low-fiber group), finding significantly reduced allergic inflammation and improved airway resistance.

Here is a blog on the microbiome and heart disease, sent out 4/8/2013:

Article in NY times today (see http://www.nytimes.com/2013/04/08/health/study-points-to-new-culprit-in-heart-disease.html?nl=todaysheadlines&emc=edit_th_20130408&_r=0 ) seems that presumptive coronary heart disease culprit of carnitine (in red meat, same Latin route at "carnivore") may be only partially correct. Published in Nature Medicine (see cad red meat TMAO nature medicine 2013 in dropbox). Turns out to (maybe) be more complex:

 

--in regular meat eaters, eating a sirloin leads to an increase in TMAO (trimethylamine-N-oxide), which in lab studies leads to accumulation of cholesterol in macrophages and and also seems to decrease the ability to excrete excess cholesterol (for excruciating detail, see the paper itself), with some previous data that blood TMAO is assoc with CAD, both in humans and mice

--in vegan who had a similar meal of sirloin (presumably with a significant bribe), no increase in TMAO.

--larger group of vegetarians given carnitine pill had no inc in TMAO.

--so, speculation that it was intestinal bacteria responsible (precursor TMA known to be produced by intestinal bacteria), and that the intestinal flora are different in vegetarians than meat-eaters -- mouse studies show that increasing L-carnitine ingestion leads to changes in intestinal bacteria.  beef has highest level of carnitine. Lesser amounts in fish, chicken, and dairy. Also in high-energy drinks for body-builders

--meat-eaters pretreated with antibiotics to sterilize colon did no have TMAO in their blood

--further analysis of 2600 pts, controlling for traditional risk factors, found that TMAO and not carnitine assoc with CAD

bottom line from these studies: you are what you eat -- diet leads to changes in the gut flora which leads to remote (and local) changes in the organism (mice and humans) and increased disease states. the concern, of course, is that there are lots of things we medical providers do which result in microbiomic changes (eg, antibiotics, colon preps for colonoscopy, suggesting certain diets such as the Adkins diet high in protein and low in fiber -- all done with the perhaps overly simplistic understanding that antibiotics are necessary (which is often not true), colonoscopy is important for colonic polyp/cancer detection (overall true, though the newer genetic tests not requiring a colon prep are pretty intriguing), and the Adkins diet is good for lowering blood sugar and weight (also true, but there may be longer term adverse effects which were not even on the radar screen when this diet was in its hayday).