Firmicutes and Obesity

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Contents

Introduction

Obesity is a major health status associated with cardiovascular diseases, diabetes, and is a leading cause of premature death in industrialized countries today. Statistics Canada report [1] shows that in 2011, an estimated 18.3% of Canadian adults qualified as obese. Approximately half of these cases had shown signs of increased health risk. Along with dietary habits and inherited risks, gut microbiota are suspected to be a key player in digestion and fat absorption. The gut of human and many other vertebrae is mostly dominated by two groups of bacteria, Bacteroidetes and Firmicutes [4]. Minor populations of Actinobacteria, Fusobacteria, and Cyanobacteria species are also present, as part of a complex microbial community [4]. Studying the relationship between obesity and the ecology of gut microbiota may provide meaningful treatments and biomarkers for susceptibility to weight gain [4].

Gut Microbiota

Importance of Firmicutes in Obesity

Past research into the correlation between gut microbiota and diet had demonstrated a complex relationship between the population of the gut and fatty acid absorption. For example, mice with normal gut micorbiota had more body fat than germ free mice who had been sterile from birth, despite the reduction in diet [4]. In particular, the abundance of Firmicutes was observed to be proportionate to the obesity levels in the mice, with the obese, conventional mice carrying significantly more Firmicutes than the lean germ free mice [4]. Along with increased fatty acid absorption, more energy was also found to be efficiently obtained from diet in the obese mice compared to the lean mice, illustrating the connection between Firmicutes and improved efficiency in energy harvesting [5].

Germ Free vs.Conventional

Diversity of Firmicutes and Obesity

Obesity is linked with phylum-level changes in the functional diversity of bacteria [11]. Functional diversity measures not only the number of various metabolic pathways, but also the abundance of each pathway. Specifically, microbiota enriched with Firmicutes demonstrated a lower level of functional diversity than Bacteriodetes-dominant microbiota [11]. Hence, obesity, which is associated with the abundance of Firmicutes, leads to an overall decrease in metabolic diversity.

Effects of Firmicutes on Host Lipid Metabolism

zebrafish

The mechanism through which Firmicutes impacts fatty acid absorption and lipid metabolism is currently best described in zebrafish. As a model organism, zebrafish not only has a similar digestive tract as mammals, but more importantly, the lipid metabolism pathway is closely related to mammals and other vertebrates [10]. The overall gut microbiota was shown to cause increases in the number and sizes of the lipid droplets. In particular, the amplification in number of Firmicutes was related to the increase in number of lipid droplets, promoting fatty acid absorption in the extraintestinal tissues [3]. This increase, however, was only evident in fed zebrafish, showing the dependency on dietary habit. On the other hand, the size of the lipid droplets increased independently of the feeding time, and was induced by other non-Firmicutes bacteria [3].

Four possible explanations were proposed in response to this directly proportional relationship between gut microbiota and fatty acid absorption. Firstly, microbes stimulate the host’s metabolism, and may increase the bioavailability of fatty acids through modifying bile salt and its production [8]. Secondly, microbes may have direct interactions and impacts on the lipolytic activities in the host [9]. Thirdly, microbes may indirectly affect physiological responses in the host’s gut, resulting in increased absorption [3]. Fourthly, microbes may cause reduction in the rate of fatty acid oxidation, which allows more absorption of fatty acid [3]. Despite the fact that the general process in which Firmicutes promotes fatty acid absorption is known, the specific mechanisms are still being explored.

Ecological Relationship between Firmicutes and Bacteroidetes

In terms of vertebrates, including humans, zebrafish, mice, and pythons, most studies conducted support two hypotheses regarding fat absorption and the number of Firmicutes in the gut microbiota.

First hypothesis is that the number of Firmicutes was observed to be diet-dependent and positively correlated to the caloric intake of the vertebrate. In zebrafish and pythons, the proportions of Bacteroidetes and Firmicutes fluctuated significantly according to whether it was fasting or being fed. The number of Firmicutes increased greatly after a meal. In humans, loss of body weight was proportionate to a decrease in the number of Firmicutes [2].

Second hypothesis is that the number of Firmicutes was found to be inversely proportional to the number of Bacteroidetes [6][7]. The number of Bacteroidetes was high during fasting, replacing the Firmicutes in the pythons ([7]. Similarly, the number of Firmicutes was notably higher than the number of Bacteroidetes in obese mice, and vice versa for the lean mice [6]. The composition of gut microbiota varies greatly with the obesity state of the organism, depicting a complex ecological relationship.

References

(1) Overweight and obese adults (self-reported), 2011, Statistics Canada, http://www.statcan.gc.ca/pub/82-625-x/2012001/article/11664-eng.htm (October 29, 2012)

(2) Ley, R.E., Turnbaugh, P.J., Klein, S., and Gordon, J.I. (2006). Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022– 1023.

(3) Semova, I., Carten, J.D., Stombaugh, J., Mackey, L.C., Knight, R., Farber, S.A., and Rawls, J.F. (2012). Microbiota Regulate Intestinal Absorption and Metabolism of Fatty Acids in the Zebrafish. Cell Host Microbe 12, 277-288.

(4) Backhed, F., Ding, H., Wang, T., Hooper, L.V., Koh, G.Y., Nagy, A., Semenkovich, C.F., and Gordon, J.I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101, 15718–15723.

(5) Turnbaugh, P.J., Ley, R.E., Mahowald, M.A., Magrini, V., Mardis, E.R., and Gordon, J.I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031.

(6) Ley, R.E., Ba¨ ckhed, F., Turnbaugh, P., Lozupone, C.A., Knight, R.D., and Gordon, J.I. (2005). Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102, 11070–11075.

(7) Costello, E.K., Gordon, J.I., Secor, S.M., and Knight, R. (2010). Postprandial remodeling of the gut microbiota in Burmese pythons. ISME J. 4, 1375–1385.

(8) Swann, J.R., Want, E.J., Geier, F.M., Spagou, K., Wilson, I.D., Sidaway, J.E., Nicholson, J.K., and Holmes, E. (2011). Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc. Natl. Acad. Sci. USA 108 (Suppl 1 ), 4523–4530.

(9) Ringø, E., Strøm, E., and Tabachek, J.-A. (1995). Intestinal microflora of salmonids: a review. Aquaculture Research 26, 773–789.

(10) Babin, P.J., and Vernier, J.M. (1989). Plasma lipoproteins in fish. J. Lipid Res. 30, 467–489.

(11) Turnbaugh, P. J., M. Hamady, T. Yatsunenko, B. L. Cantarel, A. Duncan, et al. 2009. A core gut microbiome in obese and lean twins. Nature 457:480– 484.

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