Food for Thought

The gut microbiota – a new piece of the obesity puzzle? 
Our GI (gastrointestinal) tract is home to a diverse collection of bacteria, viruses and archaea, collectively known as the gut microbiota. Patricia Lopez-Legarrea from the University of Navarra, Spain and Nicholas Fuller from The Boden Institute, The University of Sydney bring us up to date on recent research and describe a randomised controlled trial that they are undertaking to compare the effects of three different diets on microbiota composition.

Nicholas Fuller

It is estimated that a healthy adult’s gut consists of at least 100 trillion (10 to the power of 14), bacteria. It’s well known that these bugs are integral to our wellbeing – evolution has aligned our interests. ‘We are not just on friendly terms with our gut bacteria – the relationship is infinitely more intimate than that – we are married to them … we are colonised by bacteria from birth, and potentially in utero,’ writes Katrina Ray in Nature Reviews. ‘Indeed, our mothers play a vital part in providing the first building blocks for the development of our resident microbiota, jump-starting the stepwise colonisation of our intestines and the rest of the human body through skin-to-skin contact and breastfeeding. Once the gut microbiota becomes established and stabilised by age 2–3 years, these bacteria have a crucial role in nutrition and health … they have a fundamental role in synthesising vitamins and in helping to breakdown non-digestible products that provide energy to the human body.’

Recent research in humans and animals now suggests that changes to the gut microbiota composition are also related to metabolic disorders such as obesity, metabolic syndrome and type 2 diabetes.

Obesity Back in 2004, Backhed and colleagues observed that normal mice had 42% more adipose (fat) tissue compared with germ-free ones. Subsequently, they transplanted microflora from normal mice to the germ-free mice and observed that the germ-free mice had a 57% increase in their total body fat content in a period of two weeks. In 2005, Ley and colleagues observed interesting differences in the microbiota composition when they compared genetically obese mice to normal-weight mice. The obese mice showed a greater presence of bacteria with a higher expression of enzymes related to energy extraction, bowel fermentation and to the reduction in stool residual calories. In subsequent work, they transplanted the microbiota from obese mice to normal-weight mice and found that they developed obesity within two weeks. Translating the findings of these animal studies to people is now an important area of research.

Metabolic syndrome Researchers at the University of Maryland School of Medicine have identified 26 species of bacteria in the human gut microbiota that appear to be linked to obesity and related metabolic complications. These include insulin resistance, high blood glucose levels, increased blood pressure and high cholesterol, known collectively as the metabolic syndrome, which significantly increases an individual’s risk of developing diabetes, cardiovascular disease and stroke. The results of the study were published in PLOS ONE. ‘We identified 26 species of bacteria that were correlated with obesity and metabolic syndrome traits such as body mass index (BMI), triglycerides, cholesterol, glucose levels and C-reactive protein, a marker for inflammation,’ says the senior author, Claire M. Fraser, Ph.D., professor of medicine and microbiology and immunology and director of the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine. ‘We can’t infer cause and effect, but it’s an important step forward that we’re starting to identify bacteria that are correlated with clinical parameters, which suggests that the gut microbiota could one day be targeted with medication, diet or lifestyle changes.’

What next? Dietary intake is considered one of the main factors that modify the number and variety of our gut bacteria. In this context, we and other researchers from The Boden Institute at the University of Sydney are currently carrying out a 12-month, randomised controlled trial to evaluate the effects of three energy-restricted diets (500 calorie (2100kJ) per day deficit) on the composition of gut microbiota. The diets are:

• Low fat/lower GI (less than GI 55)
• High protein/moderate GI (protein 25% total energy)
• Mediterranean/moderate GI (omega-3 consumption greater than 1.3g). 

Our study consists of a 6-month intervention period with one of the three diets, followed by a 6-month weight maintenance period with visits at 9 and 12 months. We will collect blood and stool samples to perform the corresponding analyses. It is hoped that the findings will both help to pinpoint those people who will respond to dietary treatment and will optimise dietary strategies. We will be reporting our findings in about a year’s time, so watch this space.