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[FEATURED ARTICLE] The Gut Microbiome and Obesity

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Featured articles are the main stories in which the Science Media Centra Malaysia focuses in great detail on a special topic, event or person and its impact on our everyday lives. In conjunction with World Microbiome Day on 27 June 2020, Aliya Ahmad Nabil looks into the gut microbiome and its links with obesity.

FEATURED ARTICLE

By Aliya Ahmad Nabil

The human microbiota is a community of microorganisms which reside in and on the surface of the human body. The microbiome, on the other hand, refers to all the genetic material that make up the microbiota. There are separate microbiomes in different parts of the body ranging from the skin to the lungs to the gut. One of the ways the human microbiome can contribute to disease is through dysbiosis. Dysbiosis is defined as a state of imbalance in the microbiota which may result in the deterioration of health.

Regardless of whether being obese is an inherently pathophysiological (diseased) state or not, it is well-recognised that being obese puts individuals at risk for developing multiple diseases. The role of the human microbiome in relation to obesity has been the subject of numerous studies in both mice and humans.  The microbiome that has been shown to be the most relevant to obesity is the gut microbiome. This is unsurprising due to the critical role of diet in contributing to obesity and the gut being a site rich with dietary components. The gut microbiome is also the largest microbiome in terms of microbial density and diversity. Despite inter-individual differences in the gut microbiome, a core gut microbiome has been established and has been associated with maintaining human health [1].

Studies looking at obese leptin-deficient (leptin is a hormone that functions to inhibit hunger) mice and lean wild-type mice revealed that the obese microbiome has an increased energy-harvesting capacity, meaning that energy consumption is likely to exceed energy loss resulting in weight gain. Interestingly, when germ-free mice were colonised with microbiota from the obese leptin-deficient mice, they displayed a significantly greater increase in body weight than those which were colonised with microbiota from the lean wild-type mice [2]. Meanwhile, in humans it has been shown that when obese individuals were given low-calorie diets, not only did this result in weight loss as predicted, but also a shift in the composition of the gut microbiota [3].

Collectively these studies show that firstly, the gut microbiota of lean individuals differs to that of obese individuals. Secondly, the microbiota influences the chances of becoming obese. Thirdly, that this microbiome can be altered by diet.

Long-term and in some cases irreversible changes to the microbiota may be caused by the composition of one’s regular diet [4]. The changes in microbial composition are associated with different consequences and this may be a result of the different types of diet. It has been shown that the same high fat and sugar diet that results in obesity also alters the microbial populations present [4]. In contrast, high fibre diets have been found to be able to improve gut dysbiosis and prevent the adverse outcomes of cardiovascular conditions that are often linked with obesity [5].

Some may view these findings as simply reaffirming common knowledge that diet affects one’s chances of becoming obese. However, importantly these studies highlight a novel ‘missing link’ from the association between diet and obesity. This link is the gut microbiota. As such, direct manipulation of the gut microbiota may be able to prevent obesity.

What is unclear is the direction of the relationship between obesity and changes in the gut microbiome. Does obesity alter the microbiome or do changes in the microbiome result in obesity? 

Understanding these unknowns will facilitate the development of therapeutic strategies for obesity. involving the targeting of gut microbiota. Some treatment strategies that already exist include the usage of pre- and probiotics. Prebiotics are dietary compounds that have been shown to be an energy source to a select microbial genera or species that confer health benefits [6]. 

Probiotics are live bacteria that can be introduced to the human microbiota to restore disrupted microbial compositions. The effects of probiotics are debatable as there has not been consistent findings on their effects. In terms of obesity, administration of the probiotic Lactobacillus acidophilus in individuals with glucose intolerance and/or type 2 diabetes resulted in the prevention of insulin resistance [7]. Another trial involving Lactobacillus gasseri resulted in reduced body weight and BMI in the treatment group compared to the placebo group [8].

More recently, faecal microbiota transplant (FMT) has been demonstrated to be an effective way to restore balance in the microbiota. This involves the transfer of a donor faecal microbiota to the recipient. FMT has been found to be effective in the treatment of Clostridium difficile infections [9].  With regards to obesity, FMT has been shown to increase microbial diversity and insulin sensitivity [10], therefore it could help to reduce BMI. It is possible that individuals with the characteristically lean microbiome may be suitable donors for FMT in cases of obesity. However, whether these effects can be sustained long-term has yet to be confirmed.

Despite numerous studies demonstrating associations between the gut microbiota and obesity, ascertaining a direct causal link has proved to be more difficult. Furthermore, the majority of studies have been conducted in mice or small cohorts of humans. In the future, larger scale clinical trials may be able to provide more translatable outcomes. The exact contribution of different microbial populations in maintaining gut health is also unclear. Understanding this could be the key to more precise manipulations of gut microbiota to obtain favourable outcomes.  Importantly, the extent of gut microbiota contribution to obesity in relation to other risk factors has yet to be completely elucidated.

In conclusion, there is more research to be done in understanding the relationship between obesity and gut microbiota. The field is exciting and shows promise as there is increasing recognition that the microbiome is a key player in maintaining human health. The dynamic nature of the microbiota should, therefore, be exploited to the benefit of human health. Its role in exacerbating obesity given the evidence is significant enough to warrant further investigation.

References

  1. Andreasen, A., Larsen, N., Pedersen-Skovsgaard, T., Berg, R., Møller, K., Svendsen, K., Jakobsen, M. and Pedersen, B., 2010. Effects ofLactobacillus acidophilusNCFM on insulin sensitivity and the systemic inflammatory response in human subjects. British Journal of Nutrition, 104(12), pp.1831-1838.
  2. Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., Okano, M., Kagoshima, M. and Tsuchida, T., 2010. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. European Journal of Clinical Nutrition, 64(6), pp.636-643.
  3. Ley, R., Turnbaugh, P., Klein, S. and Gordon, J., 2006. Human gut microbes associated with obesity. Nature, 444(7122), pp.1022-1023.
  4. Roberfroid, M., Gibson, G., Hoyles, L., McCartney, A., Rastall, R., Rowland, I., Wolvers, D., Watzl, B., Szajewska, H., Stahl, B., Guarner, F., Respondek, F., Whelan, K., Coxam, V., Davicco, M., Léotoing, L., Wittrant, Y., Delzenne, N., Cani, P., Neyrinck, A. and Meheust, A., 2010. Prebiotic effects: metabolic and health benefits. British Journal of Nutrition, 104(S2), pp.S1-S63.
  5. Seekatz, A., Aas, J., Gessert, C., Rubin, T., Saman, D., Bakken, J. and Young, V., 2014. Recovery of the Gut Microbiome following Fecal Microbiota Transplantation. mBio, 5(3), pp.e00893-14.
  6. Sonnenburg, E., Smits, S., Tikhonov, M., Higginbottom, S., Wingreen, N. and Sonnenburg, J., 2016. Diet-induced extinctions in the gut microbiota compound over generations. Nature, 529(7585), pp.212-215.
  7. Turnbaugh, P. and Gordon, J., 2009. The core gut microbiome, energy balance and obesity. The Journal of Physiology, 587(17), pp.4153-4158.
  8. Turnbaugh, P., Ley, R., Mahowald, M., Magrini, V., Mardis, E. and Gordon, J., 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), pp.1027-1031.
  9. Turnbaugh, P., Ridaura, V., Faith, J., Rey, F., Knight, R. and Gordon, J., 2009. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice. Science Translational Medicine, 1(6), pp.6ra14.
  10. Vrieze, A., Van Nood, E., Holleman, F., Salojärvi, J., Kootte, R., Bartelsman, J., Dallinga–Thie, G., Ackermans, M., Serlie, M., Oozeer, R., Derrien, M., Druesne, A., Van Hylckama Vlieg, J., Bloks, V., Groen, A., Heilig, H., Zoetendal, E., Stroes, E., de Vos, W., Hoekstra, J. and Nieuwdorp, M., 2012. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome. Gastroenterology, 143(4), pp.913-916.e7.

Aliya Ahmad Nabil is a contributor writer for Science Media Centre Malaysia. She is a graduate from the University of Cambridge with an MPhil in Translational Biomedical Research. Previously, she was an intern at the Science Media Centre in London and also has work experience in healthcare public affairs. Her interests include science and healthcare innovation, policy and communications.

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