For Catherine Lozupone, formerly a researcher in the Knight and Gordon labs and now faculty at the University of Colorado, characterizing a ‘healthy microbiota’ or even a ‘healthy diet’ is far from straightforward.
At Experimental Biology 2015 in March, Lozupone presented her research and brought forward a provocative idea: a healthy microbiota is one that matches your diet. She spoke with GMFH after the conference to explain more.
Lozupone says recent studies that presented correlations between diet and microbiome composition found that Prevotella richness was generally associated with a healthy, lean physique and often occured in those from agrarian societies. But her research on the gut microbiomes of HIV patients didn’t seem to fit with these results.
“When we were looking at HIV patients, the same [bacteria] that had been observed with different diets in health were high in these people who were sick,” she says. High levels of Prevotella were observed in patients with HIV, who also have high rates of metabolic disease.
“[I was] trying to reconcile these observations — is having a microbiome like that good or bad for you?” she says.
The light went on for Lozupone when she read a PLoS study by Spanish researchers that, for her, answered the question of why Bacteroides are associated with both a poorer diet and being lean. “[Researchers] were feeding mice a high-fat diet and then feeding the mice (probiotically) the Bacteroides uniformis, and what they found was that Bacteroides uniformis was protective [against obesity] in mice in the context of a high-fat diet.” This meant that protective, or anti-inflammatory, bacteria were being selected for when the host consumed a poor diet.
Putting this together with the other literature, it seemed that some of the microbes were increasing in response to diet not because they were greedy for the dietary components, but because they were beneficial for the host.
“A lot of people who talk about diet — correlations in microbes — assume it’s a passive thing: the microbes that change [do so] because of their nutritional preferences,” Lozupone says. “But when we weren’t seeing these same correlations with HIV patients, it made me start to think maybe this isn’t just a passive thing. Maybe our immune system is important, playing a role in selecting for beneficial microbes in the context of diet.”
Lozupone says this means a wide range of diets could be potentially healthy, but only if your body adapts through the microbiota.
“I think certainly some diets are worse for you than others,” she says, “But there’s a personalized notion to what diet is healthy for people, why the same diet doesn’t work for everybody. The adaptive immune system of the host plays a role.”
Through this lens, health problems arising from a ‘poor’ diet can be seen as a deficit of microbial adaptation. For example, even though a high-fat diet is generally known to induce inflammation, it might not cause problems if the anti-inflammatory microbes react appropriately. “If you have bacteria that can suppress some of the inflammation that the diet is inducing, that’s going to allow you to tolerate that diet,” she says.
Lozupone says that through history, humans — the most adaptive mammal — probably had to deal with big changes in the types of foods available over time, from zebra meat to tubers. “Our bodies probably have had to evolve mechanisms to ensure that, when we’re eating different things, we digest them optimally,” she says. “These changes in the microbiome that happen with diet might not be motivated just by the nutritional requirements of the microbes but instead by the human: the host plays a role.”
This theory — which still needs more data to back it up — could one day help advance therapeutic options for obesity. “There might be different underlying reasons why [someone is] overweight. Maybe one of these is that you interact with your microbes differently,” she says. “Maybe some obese people just have a deficiency in their ability to select for beneficial microbes that can help them tolerate [their] diet.”
Lozupone sees probiotics as promising tools by which to help the microbiota adapt to different diets. “Some positive results in the literature [suggest] that probiotic administration of certain bacteria can protect against high-fat-diet induced obesity in mice,” she says, citing studies on Bacteroides uniformis and Akkermansia muciniphila. She notes that the potentially helpful bacteria are not those currently available off the shelf, however. “A recent review showed limited effectiveness of currently-available probiotics for treatment of obesity in humans,” she adds.
“There is also some evidence, again in mice, that prebiotics can encourage the growth of these bacteria and in turn lead to better tolerance of a high fat diet,” says Lozupone. “There is more work to be done but mouse experiments are promising.”