Weightloss Using Gut Bacteria
Chris - Gastric bypass surgery which reduces the capacity of the stomach is now a regular weight loss option, but new research suggests that changes to gut bacteria which follow the surgery can be as effective as changing the stomach capacity itself.
Dominic - We're joined by Dr. Lee Kaplan of the Massachusetts General Hospital to find out more.
Chris - Lee, what's actually involved in doing what we put in in inverted commas and dub a 'gastric bypass operation'?
Lee - Well, you divide the stomach, meaning you cut the stomach so that there's a small pouch made out of the top part of the stomach and that's separated from the rest of the stomach. And then you cut the bowel distally, further down, and you bring it up so that you're emptying that little pouch, that little stomach pouch, directly into the small bowel. So, the food flows through the oesophagus - the swallowing tube - into the small gastric pouch and directly into the middle part of the small bowel, bypassing the rest of the stomach and the first part of the small bowel. And in doing so, it was always thought that what you were doing was preventing people either from eating or absorbing what they ate and now, we know that actually that's not the case.
Chris - So critically, the stomach, the residuum of the stomach is left there in situ and the part of the small bowel, the duodenum of the stomach connected to it is still there. It's just that food is bypassing those two anatomical structures and going straight into a part of the small bowel, a bit downstream of there.
Lee - Exactly and even though those portions are not seeing food anymore, they seem to be very actively involved in the effects of the bypass. If you simply cut out the stomach, you wouldn't see as much of an effect as you do when you separate the stomach and leave both parts intact or both parts in the body. So, the part that's not seeing food is now sending some kind of a signal to the rest of the body. "You know what? I think we need to sort of change the balance of energy here".
Chris - And when people undergo this procedure, roughly, how much weight can they lose?
Lee - Well, the average is you'll lose about 2/3 of the excess weight. The weight above what normal would be and there's quite a bit of variation. Some people lose only half that much weight. Some people lose more than that much weight, but on average, it's a highly effective intervention. Much more effective than anything else we've got so far.
Chris - So, what was your hypothesis when you came at this study?
Lee - Well, some years ago, workers in Jeff Gordon's laboratory in St. Louis, Missouri had found that the microbiota correlates with whether an animal has, or a human being has, obesity or is thin. And further, they showed that if you take the microbiota, the bacteria that live in our bowels from an animal that is fat and you give it to an animal that doesn't have a microbiota, a sterile animal that was grown specially, that animal will gain more weight than if you do the same kind of transfer from an animal that was lean. So, we knew from those experiments that the microbiota was involved in some way in regulating energy balance, body weight, body fat, metabolic function. So we ask the question: Could the gastric bypass be working by changing the total population of bacteria that are in the microbiota? That was the premise and of course, the answer was, yes, we could.
Chris - So, how did you actually do that?
Lee - First, we asked the question of, how does the microbiota change in response to the bypass and are those changes really from the bypass or are they from the weight loss that the bypass causes? And what we found was that there's a difference in the microbiota between thin animals and fat animals. So, there's difference in the balance of different types of bacteria, but that after a gastric bypass, you actually change it even more so that you get to a third type or a specialised gastric bypass type of microbiota. And that change occurs with the gastric bypass, but does not occur when you lose weight by dieting the animals. So that's specific to a bypass. We then took the microbiota from an animal that had gotten a bypass, this changed microbiota, and we put it into another one of these sterile groups, animals with sterile gut. We found that when we did that, those animals lost weight. And again, that effect was specific to the microbiota after gastric bypass because when we did the exact same transfer from an animal that became thin because we put it on a diet, it did not have the same effect in their recipient animal. So, there's something about the microbiota from a bypassed animal that is able to cause a non-bypassed animal to lose weight.
Chris - Do you know what's actually going on as a consequence of the operation to trigger that change in the bacterial population that then has this onward effects?
Lee - Well, that's a great question and we don't really know the answer. We have hypotheses that the changes in the structure of the gut cause a whole variety of signalling changes. We think that bile acids which are secreted into the lumen of the gut play a role. We think that the mucus layer of the gut, the mucus line, the wall of the bowel plays a role. Just because of the nature of the changes of the bacteria, some of those bacteria that are favoured after bypass preferentially get their energy from that mucus layer. But we don't really know the answer to that. One thing that's important to note however is that the biggest changes that we saw in the microbiota were in the bottom end of the bowel, in the ileum and in the colon which is far removed from where the surgery was. So of course, if you only had changes in the microbiota right where you operated, you might imagine it was some kind of a technical fluke. But here, we're seeing that throughout the bowel, and actually many other parts of the body, the microbiota fundamentally change. So this looks like a systemic effect but we don't yet understand why.
Chris - The obvious aspiration is to be able to produce that effect without having to do that fairly dramatic and in many cases, life threatening surgery.
Lee - Exactly. I'm not a surgeon but I do take care of many patients who get the surgery. It can be life threatening. Although I have to say that it's a valuable intervention when used in the appropriate patients. In the United States at least and it's actually less in the UK, but in the United States, only 1 in 400 patients with obesity get a gastric bypass. So, rather than thinking about substituting something else for a gastric bypass, I'm much more interested in focusing on those 399 that are not receiving any effective therapy. So, if we could harness the "magic source" of a gastric bypass without the bypass, we could perhaps apply it to some of those 399.
Chris - Lee, thank you very much. That's Dr. Lee Kaplan from Massachusetts General Hospital.