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Is the microbiome the key to obesity?

27th September 2023

The microbiome is the latest research frontier in obesity and the latest studies – and future speculation – were under discussion at the recent American Diabetes Association’s 83rd Scientific Sessions. Dr Susan Aldridge reports. 

There are around 20,000 genes in the human genome, but the human microbiome consists of two million to 20 million genes – this means that, until recently at least, we have not taken much account of around 99% of the genetic material in our bodies. “What’s most shocking about this is that the genes in the microbiome are the ones we can change,” said Professor Rob Knight from Rady Children’s Hospital at the University of California, San Diego. “If we could take control of that process, it could have a very profound impact on many aspects of our health.” 

Professor Knight, who directs the Center for Microbiome Innovation at the University, went on to discuss some of the research he and others are doing in this area. For instance, predictive models for health-relevant traits, including obesity, can now be built from our human and microbial genes. “For the last decade, I’ve been able to tell from the genes in your gut whether you are lean or obese with about 90% accuracy, but only with 57% accuracy from the human genome itself,” he said. Studies have shown that the microbiome is associated with traits that are relevant to obesity and diabetes, such as waist circumference, LDL-cholesterol, HbA1c and body mass index (BMI). 

Faecal transplants or diet?

If you transplant the gut microbiome from an obese mouse to a lean mouse, the recipient becomes obese. Similarly, on transplanting the microbiome of a lean mouse, the recipient remains lean. Furthermore, the same results apply if the transplant to the lean mouse is from the microbiome of an obese or lean human, demonstrating a causal link between the microbiome and obesity in a mammalian model.

These findings also apply in inflammatory bowel disease, Parkinson’s, autism, colon cancer and multiple sclerosis. “You can transfer these phenotypes from humans to mice, but we still need to prove the underlying mechanisms and which microbes and metabolites are involved,” said Professor Knight.  

The human vaginal, oral and faecal microbiome can all be mapped now and experiments show that you can alter a recipient’s microbiome from an unhealthy to a healthy state by transplantation, which shows that the donor had a healthy phenotype. “The question is, can we bring the patient back to health with the right donor?” asked Professor Knight, adding that this may turn out to be the wrong approach, in obesity at least.    

Maybe, then, our attention should turn to diet and changing our microbiome from the inside. “Food is a language that speaks to our genes,” said Professor Knight. “How our genes are expressed depends upon what we eat.” However, nutritional research is difficult. In one study, covering 120,000 people tracked for 20 years, the effects of specific food items on weight gain and loss was reported. The food most associated with weight loss over a four-year period was yogurt, while French fries were most associated with weight gain. A daily serving of either food led to weight loss of 0.82 lb and weight gain of 1.69 lb, respectively, over the four years. “So if you swap the fries for yogurt, you’ll only lose two pounds, which is not much reward for such an effort,” said Professor Knight.  

However, people do vary in their individual response to foods. One study has shown that people eating identical meals show very individual post-meal glucose responses. “A food that would cause one person’s glucose to spike was totally OK for someone else,” noted Professor Knight. So, for instance, for some people, ice cream was better than rice and for others vice versa – and it is the gut microbes that ‘decide’ the glucose response in each case. 

A test has now been developed to determine if someone is in the rice or ice cream category. This begs the question of whether you could modify your gut microbes in order to modify your glucose responses to foods such as rice or ice cream, which ultimately could help tackle obesity through a personalised diet. Such microbiome interventions are already saving lives in cancer, where dietary fibre and probiotics have been shown to influence the response to immunotherapy for melanoma.  

Towards a ‘smart’ toilet?

The real challenge is building a ‘user interface’ for our microbiomes. “At the moment, it’s very hard to understand what you should ask people to do,” said Professor Knight. “But maybe one day, you’ll have a smart toilet which, as soon as you flush, delivers your microbiome sample for the day and gives you some sort of display, so you can see how your microbiome’s developing.” You can plot the microbiome composition over time and see a trajectory, so people could be told, with real-time feedback, whether they are going in the right or wrong direction and what they can do to change things. 

“You could modify your microbiome through very precisely targeted dietary interventions,” said Professor Knight. “Maybe artificial intelligence (AI) could even be involved in this and you could ask questions like ‘should I eat regular potatoes or sweet potatoes, wholegrain or white bread?’ – things that have been shown to have different effects in different people with respect to glycaemic index. We are working to solve this problem, to give you something useful you can do with your microbiome. So, in conclusion, the microbiome may be the key to obesity, but we have to know how to use it to unlock the right door.” 

To learn more about the link between obesity and type 2 diabetes, enrol on the EASD e-Learning course ‘Obesity and diabetes’.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.