Bacteria in poop: the key to losing weight?

Summer is officially over and, temporarily, we don’t need our summer bodies. However, losing weight is not just about looking nice on sandy beaches; obesity is one of the key risk factors that causes cardiovascular disease and other chronic diseases.

Obesity is a multi-facet condition: genetics, activity level and diet all contribute. Solutions to this issue are obviously to exercise and eat healthily. On the extreme side, surgery is also an option. However, associated risks can be severe, and therefore only morbidly obese individuals are offered this treatment in the UK.

Recently, the role of the immune system in obesity has also been investigated. There are many different populations of microorganisms living in our digestive tracts, known as gut flora. The relationship between gut flora and us can be beneficial; some help us digest dietary fibre in vegetables, breaking it down so we can absorb it. Gut flora also produce vitamin B and K for us and prevent the growth of harmful organisms.

Nevertheless, like a well-organised company, this beneficial effect only works with a specific population of flora. In a company, we need a certain number of employees, each with different talents and roles. That way, the company can efficiently carry out its daily routine. If most of the employees decided to quit one day, the company would face crisis and less ideal candidates may be hired to keep the company going.

Antibiotics, like an economic crisis to our imaginary company, can wipe out the good bacteria and affect the host’s ability to digest food. The absence of these florae may also fail to stop pathogens from growing, leading to diarrhoea. Furthermore, it has also been shown that people who are obese have a different gut flora profile. While it is unclear whether the shift in gut flora population causes obesity or the other way around, there is certainly a clear association between the two.

The shift in gut flora profile activates the immune system, exacerbating the situation and increases the risk of cancer and autoimmune diseases. A research group in the University of North Carolina has tried to manipulate the immune system in mice to investigate its effect in obesity. They suspected that high-fat diet induces the imbalance of the delicate gut flora ecosystem by increasing inflammatory response in the body.

NLRP12, a leucine-rich repeating protein (NLRP), is a mediator of the immune system and promotes the resolution of inflammation. Nonetheless, its role in obesity is unknown in reality. To investigate, the researchers hypothesised NLRP12 can reduce weight gain by damping down the immune system and reducing inflammation to the gut and fat tissue whilst the removal of this protein would have the opposite effect. Putting the theory to test, the scientists knocked out the gene coding for NLRP12, so the mice didn’t have these receptors in their cells.

As a result, these knockout animals were relatively fatter despite having the same diet and lifestyle as the control group. These mice were also less sensitive to insulin, making them more susceptible to diabetes. The obese mice also had more immune cells in their fat tissue, with a very specific pro-inflammatory cell population (M1 macrophages). Elevated levels of pro-inflammatory cell signalling molecules, like TNF (tumour necrosis factor) and IL-6 (interleukin-6), which are released from the fat tissue, were also found in the obese mice.

Furthermore, analysing the gut microbiome in the mice, they found that mice with a high-fat diet and NLRP12 knockout had a lower bacterial diversity in the intestine, correlating to inflammation and obesity. Faecal transplants from obese mice to other mice also promote weight gain and putting normal and knockout mice together in one cage can reduce obesity in the knockouts by coprophagic-transfer of microorganisms (poop-eating). Upon analysing the population, the researchers also identified families of bacteria that are more predominant in obese mice, namely, the Erysipelotrichaceae promotes weight gain. Contrarily, the Lachnospiraceae family seemingly has a beneficial effect on weight loss.

While faecal transplant seems unhygienic and difficult to implement in humans, chemical products that the good bacteria produce could potentially be packaged as supplements to treat diabetes and obesity. Though more experimental data is required to verify the beneficial bacterial population, this strategy is certainly a relatively inexpensive and easy (in terms of lifestyle changes) solution.