Saturday, May 25, 2013

Redefining the gutsy scientist

This past week, I was fortunate enough to meet the microbiologist Liping Zhao. His research looks at how the gut microbiome - or totality of microbes in/on an area of the body and their interactions with that part of the body - is affected by diet. While many other groups have tried to find a relationship between human health (obesity, diabetes, heart disease) and gut microbes by comparing individuals, Dr. Liping Zhao is one of only a handful of researchers who directly test how changes in diet which affect health are mediated by microbes - he attributes this to the holistic nature of Chinese medicine.

Perhaps his best-known study is the one he completed on himself. He was overweight, so he decided to eat the fermented foods Chinese yam and bitter melon, which are thought to change the microbes in the gut, along with a whole grain-rich diet. He lost about 45lbs over the course of two years, and a single type of bacteria called Faecalibacterium prausnitzii and known for its anti-inflammatory properties flourished during this time. Liping confirmed that this bacteria was associated with reduced inflammation by comparing levels of the bacteria to levels of compounds in urine associated with inflammation in two American and Chinese families.

Look into my gut. You are getting healthy. Very, very healthy.

All of this fits nicely into the idea that obesity and diabetes are essentially inflammatory diseases, mediated by changes in gut microbiota which become increasingly irreversible. The story goes somewhat like this. Beneficial microbes dominate in the healthy gut, and we have evolved with these microbes for many years. However, the modern (low fiber, high sugar, high fat) Western diet isn't quite right for these microbes, which allows other bacteria which may or may not have previously been hanging out in the gut to do better. These bacteria aren't ferocious acute disease-causing bacteria like Salmonella or E. coli 0157:H7, but rather have much subtler effects. Bacteria have different surface sugars, fats, and proteins which are recognized by the host immune system to different degrees, with less or no response to the surface of long-resident beneficial microbes, but a strong response to microbes not seen by the host before (unless the bacteria is also producing something to pervert this response, but that's another story :-)). This leads to inflammation, which makes the gut wall a bit leakier, so more toxins produced by these bacteria can get into the bloodstream and cause inflammation elsewhere. Another argument is that in already obese people, the fat cells are too big and so cannot get enough oxygen and die, recruiting immune cells to the scene.  Either way, cells are less responsive to insulin, and therefore less able to take up glucose, eventually leading to type 2 diabetes.

Perhaps more interesting, though, is the idea that Liping had that we might be able to predict whether a person is pre-diabetic before symptoms appear, by examining the microbes in the gut. There is a small problem with this idea, however, and that is that the microbes in people's guts differ greatly, and a wide variety of gut microbiomes can be considered healthy. To fix this problem, Liping suggested using samples collected as part of the annual health checkups completed for all workers in some businesses in China; this would allow him to follow how the microbiome changes through time and determine the range of microbiota possible before a person becomes "unhealthy". This is definitely a study I would like to see followed through on.

As a final note comes a study which must be incredibly marketable to the American-pill-popping public. In looking for microbes responsible for health in his own gut microbiota, Liping decided to try other traditional remedies for reducing obesity. One of these is berberine, which is a compound found in the yellow berries of those super annoying spiky barberry bushes grown ornamentally in Britain, and which are serious invasive species in New Zealand. Liping fed this compound to a series of obese mice, along with a whole-grain rich diet, and found massive weight loss and increased glucose sensitivity in the patients. When he took gut microbes on a plate and just poured berberis over them, they didn't die at the low doses needed to drastically improve host health, which indicates that berberis may have been acting to change the competitive interactions between gut microbes in such a way as to favor those beneficial ones again. The good news for the american consumer is that berberine is available in tea and pill form. But rumor has it that drinking the tea is like drinking pure warheads.  But maybe it is worth it. Easier than exercise, eh?

Could this be the future of slimming?

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