Relationship between the Microbiome and Obesity

Abstract

Obesity is a major public health concern. While the association between caloric intake and body weight has been understood for years, the link between human microbes and obesity is a relatively new concept. As new information emerges, scientists are beginning to call the gut flora the “forgotten organ”, and for good reason. This narrative review will examine the relationship among the microbiome and obesity through twin studies, animal models, genetic links, and antibiotic use.

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Introduction

Rates of obesity have been climbing at a steady pace since the 1970’s. As of 2016, almost 40% of adults in the United States were obese (Fox, Fang & Asal, 2019). Obesity rates are only expected to keep rising; in some states the obesity rate is expected to exceed 60% by 2030 (Sturm & Hattori, 2013). Years of research has led to an overall good understanding of the causes of obesity such as diet, exercise habits, genetics, etc (Friedman, 2009). Thus, obesity is a biobehavioral condition. Although, new research has been emerging regarding the role of the microbiome when it comes to obesity.

The microbiome is the community of living bacteria that is present within human tissues such as the gut, gastrointestinal tracts, placenta, etc. The human gut alone is known to contain between 10 trillion and 100 trillion organisms (Mikkelsen, Frost, Bahl, Licht, Jensen, Rosenberg & Knop, 2015). The bacteria have a symbiotic relationship with the gastrointestinal system in that it aids in digestive processes, maintaining the immune system, synthesizing vitamins, and fermenting unused energy (Parekh, Balart & Johnson, 2015), (Knight & Girling, 2003). There are about 1,100 different strains of bacteria and archaea all together. At any given time, each person hosts an estimated 160 different species of bacteria (Tilg & Kaser, 2011). There are many aspects of daily life that can influence an individual’s gut bacteria such as diet, environment, and genetics. As new research emerges, it is becoming apparent that some types of bacteria are associated with certain health conditions such as liver disease, mood disorders, arthritis, etc (Sidhu & van der Poorten, 2017). Most importantly, findings consistently exemplify a relationship between certain strains of bacteria and obesity.

Similarities in Gut Microbes Among Obese Individuals

A few studies have been conducted which explore the differences in gut microbes amongst obese and lean individuals. Obese individuals are classified as anyone with a BMI of 30 or greater. An individual considered to be normal weight is anybody with a BMI of 25 or less (Elsayed, Davis, Dupépé, McCluggage, Szerlip, Walters & Hadley, 2017). One study that examined microbes from lean and obese twins found that scientists were able to classify individuals as lean or obese with 90% accuracy from looking at their gut microbes alone (Knights, Parfrev, Zaneveld, Lozupone, Knight, 2011). In order to distinguish lean individuals from obese individuals, researchers had to make observations regarding which types of bacteria were more prevalent in individuals with different body weights. Studies regarding obesity and gut microbes consistently find that obese individuals have less diverse gut bacteria compared to lean individuals (Kasai, Sugimoto, Moritani, Tanaka, Oya, Inoue &Takase, 2015).

Furthermore, when comparing sets of twins who were lean and obese it was found that 75% of obesity enriched genes were from Actinobacteria compared to 0% of lean-enriched genes being from Actinobacteria. Meanwhile, 42% of lean-enriched genes came from Bacteroidetes compared to 0% of obesity-enriched genes coming from Bacteroidetes (Turnbaugh, et al, 2009). These exact percentages may not be representative of the entire population but rather serve as trends.

Researchers have compared each individual’s gut microbiome to an individual island. Each individual has unique set of microbial phylotypes like each island consists of different species with shared cored functions (Doolittle & Booth, 2016). Although unlike islands, an individual’s microbiome can be changed. These changes occur based on various lifestyle factors.

Animal Models

Some of the very first instances of research regarding the malleable nature of the microbiome in relation to obesity was done on animals, specifically mice. Fecal matter is a good indicator of what our microbiome looks like on the inside. Thus, some researchers examined the fecal matter in relation to the gut bacteria profiles of obese mice and lean mice. It was found that different bacteria correlated with different phenotypes (Greenhill, 2015).

Interestingly, fecal matter can be transplanted. When fecal matter was transplanted from obese mice to lean mice, the lean mice began to show characteristics consistent with the obese mice (Magrini, Mardis, Mahowald, Ley, Gordon & Turnbaugh, 2006). The results were consistent when reversed, in that obese mice demonstrated characteristics of weight loss when given fecal transplants from lean mice. This phenomenon is attributable to Lactobacillus plantarum; a few strains of Lactobacillus plantarum bacteria have been identified for their anti-obesity effects throughout multiple studies (Angelakis, Merhej & Raoult, 2013), (Drissi, Merhej, Angelakis, El Kaoutari, Carrière, Henrissat & Raoult, 2014), (Deng, Lyon, Bergin, Caligiuri & Hsueh, 2016). Mice studies prove that the obese phenotype is transmissible with gut bacteria (Ellekilde, Selfjord, Larsen, Jakesevic, Rune, Tranberg & Hansen, 2014;2015).

Another animal study examined the fecal bacteria of flounder. Researchers sought out this species because they eat communally, thus minimizing the variation in their diet. Diet is known to play a big role in obesity. Investigating a species where diet was the same allowed them to examine relationships among other factors on obesity without confounders, such as genetics (Turnbaugh, Hamady, Yatsunenko, Cantarel, Duncan, Ley, 2009). It was found that 13 different types of bacteria had evidence of heritability (Davenport, Cusanovich, Michelini, Barreiro, Ober, & Gilad, 2015). There are currently no replications of the study on humans, which raises questions as to whether patterns of genetic inheritance could be attributed to our gut bacteria such as it was in the flounder population.

Genetics and Microbiota

While research regarding genetics and gut microbiota is relatively new, researchers are confident regarding a few aspects of the role of our parents in our gut microbes. Many studies have shown that a child’s first bacteria is inherited from their mother while in the womb and during birth. Specifically, the dominant strain of bacteria found within the mother (via fecal examination) was found to be most prominent when it came to the child’s microbes. The mother’s secondary strain was found to preferentially colonize the gut of her child (Yassour, Jason, Hogstrom, Arthur, Tripathi, Siljander, Xavier, 2018).

As mentioned earlier, certain types of bacteria strains have been associated with their obesity, while others have anti-obesity effects (Tsai, Cheng & Pan, 2014). Therefore, we can begin to understand why we so often see an association between the phenotypes of a mother and her offspring. Although, bacteria can be wiped out from our systems as easily as it is established.

Antibiotics

One way that bacteria can be removed from human systems is antibiotics. Antibiotics are highly prevalent in the United States (Olesen, Barnett, MacFadden, Brownstein, Hernández-Díaz, Lipsitch, & Grad, 2018). The CDC (2017) reports that in 2017, some states have over 1,000 antibiotic prescriptions per every 1,000 individuals, meaning that on average, every individual took an antibiotic at least once.

Antibiotics work by fighting infection. In order to get rid of infections, antibiotics kill the “bad” bacteria that causes the infection. Although, antibiotics cannot distinguish between the bad bacteria and good bacteria (Lin, Zhou, Steitz, Polikanov, Gagnon, 2018). There is growing evidence that indicates antibiotics can change the make-up of the gut microbiome thus contributing to changes in body weight (Dutton, Doyle, Buchan, Mohammad, Adamo, Shorr, & Fergusson, 2017).

In one human study, individuals were given antibiotics over the course of 4 days. Their gut microbes were examined before and after taking the antibiotics. It was found that there were dramatic reductions in the gut bacteria after taking the antibiotics (Mikkelsen, Frost, Bahl, Licht, Jensen, Rosenberg & Knop, 2015). Furthermore, the measured symptoms on the subjects were gastrointestinal symptoms and slightly reduced tAUC_insulin on day 4. This study demonstrates the short-term impact that antibiotics have on the microbiome.

Other studies investigated the long-term impact of antibiotic use on obesity. 362,550 children who had the same height and weight measurements at birth were followed for 5 years. It was found that children who received an antibiotic prescription when they were under 24 months had slightly higher odds of being overweight or obese with an odds ratio of 1.05 (Block, Bailey, Gillman, Lunsford, Daley, Eneli,, 2018).

Further research is needed to determine exactly how antibiotics play a role in gut microbes and obesity. Due to the fact that obesity is a biobehavioral condition, many other lifestyle and genetic factors are simultaneously influencing gut microbes and body weight. Although, researchers can say with certainty that antibiotics essentially wipe out gut microbes, allowing for new bacteria, sometimes those deemed as “bad”, to overpower the gut. Bad bacteria is the bacteria that can cause infections, disease, or even promote obesity.

Conclusion

While our microbes are not the sole factor in obesity, they relate to many things that are linked to the biobehavioral characteristics of obesity. Genetics, environment and lifestyle factors are all factors known to play a role in body weight (Arteaga, Esposito, Osganian, Pratt, Reedy, & Young-Hyman, 2018). This narrative review has explored ways that microbes are simultaneously associated with all of these things. For example, microbes have shown to have aspects of genetic inheritance when it comes to animal models and humans. In addition, societal norms such as antibiotic use can alter gut microbes; this allows it to become relatively easy for new forms of bacteria to colonize the gut. Overall, the research regarding the microbiome and obesity are still relatively new. Looking to the future, there seems to be promise for the integration of bacteria when it comes to obesity treatment.

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