MY WORLD OF TRUTH

Our guts contain around 100 trillion microbes, collectively known as the gut microbiota. No two people’s microbiomes look exactly the same, and they are a product of what we inherit from our mothers during birth, our diets, environment and lifestyle.

It is well established that the gut plays a role in numerous systems in our body, including digestion, hunger and satiety, through multiple mechanisms, but now researchers are starting to uncover the specific differences between the microbiomes of obese and lean people, and develop personalised weight-management treatments based on their findings.

There are hundreds of differences in the human genome that predispose us to obesity, which increases the risk of developing cardiovascular diseases and type 2 diabetes, and is increasing in most countries around the world.

Studies involving twins have shown that obesity has a heritability rate – how much variation in traits is caused by variation in genes, rather than the environment – of between 40% and 75%, which means there is room for external factors to play a role. But while there are many differences in gut bacteria that could influence weight, scientists don’t yet know why, or even how much of it comes down to our genes.

Some dieters struggle more than others to lose weight, despite following sensible advice, and this may come down to the bacteria in our guts. Specifically, the enzymes carried within it.  

“What we eat is available to us, and to the bacteria inside our guts, which digest parts of food we lack the enzymes to do,” says Purna Kashyap, associate professor at the Mayo Clinic and head of its Gut Microbiome Laboratory.

“This process generates additional calories that the gut microbiota can give back to us, so it’s a mutually beneficial relationship where bacteria give us more bang for our buck from what we eat,” he says.

Kashyap tested to see if, when switching to a lower-calorie diet, gut bacteria can be more efficient in deriving calories from food, which would be helpful when food isn’t plentiful, but could also hinder weight loss.

In a pilot study, 26 participants went on a lower-calorie diet high in fruit and vegetables, and some didn’t lose as much weight as others. Analysis of their gut bacteria found participants had different levels of two particular types of bacteria, and one, Dialister, that hindered weight loss.

In those unable to lose weight, this bacteria was able to break down carbohydrates and use their energy. more effectively, Kashyap says.

However, Kashyap says that only a fraction of weight loss can be controlled by these microbes.

“It makes biological sense that the bacteria may be hindrance, but they can only play a small role as they produce only a small number of calories needed.”

While the research couldn’t conclude where Dialister comes from, one study found that some bacteria we get from our diet could indirectly cause weight gain by changing the gut’s behaviour.

Researchers analysed the blood plasma and stool samples of 600 obese and non-obese people, and found 19 different metabolites linked to four types of gut bacteria that could lead to weight gain, including glutamate, linked to obesity, and BCAAs (branched chain amino acids), associated with higher insulin secretion and risk of type 2 diabetes and cardiovascular disease.

These metabolites may be partly determined by meat consumption, according to researcher Louise Brunkwall.

“The metabolite pattern that we identified contained a lot of branched chain amino acids, which are found in animal products. This is in line with other research that show that a high protein intake increases the risk for several diseases.”

Brunkall says research needs to focus on how the composition of gut bacteria can be modified to reduce the risk of obesity, as well as understand what a healthy gut looks like, and what factors change its bacterial composition.

There is no clear picture yet of the differences in the gut bacteria profile of lean versus obese people, says Oluf Pedersen, professor of Metabolic Genetics at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. But what is being established is the importance of having a diverse intestinal microbiota, filled with many different types of bacteria.

Pedersen and his team analysed the gut bacteria of 123 non-obese and 169 obese adults, and found that the 23% of those who had a comparatively low diversity were more likely to be obese, have insulin resistance and elevated blood lipids, and increased levels of inflammation markers in the blood, all of which increase the risk of type 2 diabetes and cardiovascular disease. Those who were both obese and had lower bacterial diversity gained much more weight over the previous nine years.

Pedersen says the reasons some people have more gut bacteria diversity than others isn’t yet understood, but scientists do know that having multiple antibiotic treatments can contribute to a major loss of bacteria that never fully recovers.

It isn’t fully established whether diversity of bacteria is a cause or consequence of weight gain, however, there is evidence that the microbiome can influence metabolism.

One study found that we may be able to achieve higher gut microbiota diversity by increasing our fibre intake. When we consume fibre, our guts break it down into short chain fatty acids, including butyrate, an anti-inflammatory linked to leanness and lower inflammatory diseases, explains Ana Valdes, author of the study and associate professor at the University of Nottingham.

“If people with type 2 diabetes go on a high-fibre diet, you can reduce their diabetes status and increase butyrate production,” she says.

“People who have more diverse microbiomes and eat more fibre have less insulinogenic diets (consisting of foods that give us lower spikes in glucose and insulin), and probably have higher energy expenditure.”

“We need to test this properly, but gut bacteria could convert the fibre into substances that modulate insulin sensitivity and energy metabolism.”

Recent, and arguably the most ground-breaking research into the link between weight and gut health so far involves the bacterial species Christensenellaceae. Around 97% of us have detectable levels of the bacteria in our guts, but it has been found to be more present in lean people.

When researchers looked at heritable gut microbes, Christensenellaceae came top of the list, found in gut microbiomes around the world and showing up from a very early age, including in the guts of babies.

“We’d never heard of it before, and we pride ourselves on knowing names of things,” says Ruth Ley, lead researcher on the study and director of the Department of Microbiome Science at the Max Planck Institute for Developmental Biology.

“We had to go back and look at where it had been this whole time, but it had only just been named so it wasn’t searchable by name, only by sequence,” she says.  

Researchers transplanted an obese-associated microbiome, amended to include Christensenellaceae, into mice and found that it protected them against weight gain.

“Since host genetics only account for around 40% of relative abundance, we don’t know where 60% of Christensenellaceae is coming from,” says Jillian Waters, who was part of the research team who discovered the bacteria’s ability to protect rats from gaining weight. She has a hunch it comes from our diet and lifestyle, and now, researchers are trying to get to the bottom of what it actually does and where it comes from, to pave the way for future treatment.

In the meantime, researchers from the Weizmann Institute in Israel have found a way personalise treatment to benefit gut health and lower the risk of developing diabetes, which is associated with obesity. 

Researchers recruited 1,000 participants, and tasked them with measuring their blood sugar every five minutes and recording their diets, how they slept and felt for one week, and found that they reacted differently to different foods.

“Many foods created the reactions we’d expect in people, for example, eating meals without any sugar kept blood sugar constant in most people, and sugary foods made levels spike, but the degree to which this happens varies greatly between people,” says Eran Segal, lead scientist on the project.

“Tomatoes are one food that spikes levels quite a lot for some people, so the amount they eat should be controlled, while others may find a single food is bad for them but, when combined with another food, might be better.”

From the data they collected, the researchers developed a computer algorithm that could take a person’s gut bacteria composition and predict how their blood sugar levels will react to different foods. They tasked 25 participants with eating food deemed ‘good’ for their blood sugar for one week, then food deemed ‘bad’. The diets changed their blood sugar reactions and successfully balanced blood sugar levels.

Our gut bacteria and individual blood sugar responses to different foods may evolve over time, Segal says, but this would take a long time, and our guts before and after changes would still be more similar than how our guts compare to another person.

The algorithm has been licensed to start-up Day Two, which offer services in Israel and US, and is planning to expand to the UK in the near future. Segal is now conducting research on people with pre-diabetes and diabetes and is seeing that personalised diets designed through the algorithm, when maintained for a longer period, can reverse both pre-diabetes and diabetes.

Researchers are hopeful that other personalised treatments will be available in the next five years – but there is a lot of work to do yet.

The bacteria in our guts, says Kashyap, are capable of complex biochemical reactions.

“We now need to understand how these bacteria influence each of these processes, leading to obesity and diabetes, which are complex, multifactorial diseases.

“The microbiome is changeable, we can modify it. If we can figure out how gut bacteria is driving it, we should be able to target it at multiple levels, which will each have an impact on treatment of obesity. There’s no doubt the microbiome is a part of that solution.”