The Microbiome and Obesity
The first study to link the microbiome and obesity was using leptin deficient mice (mice that cannot produce leptin molecule that signals satiation and so become obese).
Obese mice were found to have broad phylum-level changes in microbial community with increased Firmicutes and decreased Bacteroidetes.
The amount of energy extracted from food was examined in the lean and obese gut community.
One of the most beneficial activities of the microbiome is to digest molecules in food that the body cannot. Microbes contain genes that produce enzymes that digest foods such as complex polysaccharides. We do not possess such genes,
From an evolutionary perspective, microbes allowed us to extract the maximum amount of energy from food consumed. This is a helpful feature to have in a hunter gatherer society.
Microbes in the obese gut community can extract significantly more energy from diet than those in the lean community. The community was enriched by genes for energy harvesting, especially for carbohydrates and lipids. Therefore energy consumed increased. We have the same genes as our hunter gatherer ancestors but now there is more food around.
It is important to note that these experiments prove correlation and not causation! Changes in the microbial community are correlated to obesity and may not be causing it.
Experiment 1
Gnotobiotic mice are raised in a bacteria-free environment and are not colonized by microbes. Bacteria are then transferred from obese mice and lean mice to the Gnotobiotic mice. Over 2 weeks, the Gnotobiotic mice became fat from the obese bacteria even though both sets of mice were eating the same amount of food.
The microbes from the obese mice were able to extract more energy from the diet compared to those of the lean mice. This proves a mechanistic link between altering the microbiota and obesity
Experiment 2
The microbiome is also linked to behavioural changes in relation to obesity/leanness
The immune system has receptors that help the body recognise bacteria. These proteins are called Toll-like receptor 5 (TLR5).
Scientists can raise mice that don’t have this protein called TLR5 knockout mice (as opposed to wild-type mice). They can then examine how obesity, blood pressure and insulin resistance are affected by mice lacking the TLR5. Faecal samples were transferred from both types of mice to new mice. Those from the knockout mice caused the mice to experience increased hunger and to eat more food than in the wild with the result of increased weight gain.
The importance of genetic richness
This is very important. Researchers analysed genes from lean and obese individuals.
Lean individuals harbour microbes that had the greater number of genes, whereas obese individuals had lower gene counts.
Obese communities featured:
- Reduction of butyrate-producing bacteria;
- Increased potential to degrade mucus lining of gastro-intestinal tract
- Reduced hydrogen and methane production
- An increase in Campylobacter/Shigella abundance;
- An increased potential to manage oxidative stress (peroxidase).
Overall, this suggests that individuals with a low gene count (low richness) harbour an inflammation-associated microbiota: Le Chetelier et al 2013, Nature
Sections
How we study the Microbiome Part 1
How we study the Microbiome Part 2
The gut microbiota, autoimmune diseases and allergies
Human Microbiota and Gut Disease