Alexandra Grbcich

Brannan
Nutrition 2200
6 November 2014
Gut Microbiota: Relation to Obesity, Metabolic Disease, Appetite, and Epigenetics
A growing interest has arisen on the importance of the microbiota living
inside the gastrointestinal tract within the past few years (Elli, Taglibue 2012).
Studies have been conducted on the makeup of gut microbiota and its relationship
to obesity, metabolic diseases and epigenetics. Obesity and other metabolic diseases
are increasing worldwide, increasing by 75% in the past 25 years (Dibaise, Frank,
Mathur 2012). The health problems associated with excess adiposity are putting a
greater importance on public health, and encouraging investigation to the
underlying problems (Elli, Taglibue 2012). For decades, genetic changes were
thought to be the main causation of health and disease (Arkadievich 2012). Within
the past decade, it is becoming clear that any phenotype results from complex
interactions between genotype, epigenome, and the environment (Arkadievech
2012). The recent obesity and related diseases epidemic is likely to be programmed
into humans through selective pressures, with research showing gut microbiota as
critical factor of nutrient uptake, energy regulation, weight and metabolic disorders
(DiBaise, Frank, Mathur 2012).
The first definite evidence of the role of gut microbiota came from a group of
experiments with germ-free mice, which are mice that are raised without the
presence of microorganisms (Musso, Cassader, and Gambino 2010). The germ-free

mice were found to have 40% less body fat compared to conventionally raised mice,
even though their calorie intake was 29% higher (Cassader, Gambino, Musso, 2010).
Within two weeks, the germ-free mice intestines were conventionalized with
cecum-derived, distal microbial communities (Cassader, Gambino, Musso 2010).
After conventionalization, the mice gained 57% more body fat compared to when
they were germ-free.
Endotoxaemia and low-grade inflammation caused by gut microbes are
related in the onset of metabolic disorders that are associated with obesity
(Everard, Cani 2013). Mechanisms of intestinal microbiota include the provision of
additional energy through the conversion of dietary fiber to short-chain fatty acids
which effects on the gut-hormone production, and increases intestinal permeability,
which causes elevated systemic levels of lipopolysacchardies (LPS) (Blaut, Klaus
2012). Very recently, a slightly controversial cure for obesity has begun to be tested.
Fecal transplants, bacteriotherapy, or human probiotic infusions have been a
popular topic of discussion in the recent years due to the success of bateriotherapy
treating the hospital acquired c.diff infection (Luiggi 2010). Researchers found a
pair of identical twins were one twin was lean, and the other was obese (Kolata
2013). Gut microbiota was transferred from the twins into mice, and found the
microbes from the obese twin made the mice obese, while the microbes from the
lean twin kept the mice lean (Kolata, 2013). After five weeks of observation, the
mice with the obese twins microbes gained 15-17% more body fat, and had
metabolic changes associated with obesity compared to the microbes given to mice
from the lean twin (Kolata, 2013). Researchers suspect microbes in the gut play a

role in human obesity, but it has not yet been proven fecal transplants in humans
treat obesity (Kolata, 2013).
Microbiota has been proven to have an effect on the food we crave, dietary
habits and appetite (Alcock, Aktipis, and Maley 2014). There is circumstantial
evidence for a connection between cravings and makeup of host gut microbiota
(Alcock, Aktipis, and Maley 2014). People who suffer from chocolate cravings have
found to have different microbial metabolites in their urine compared to chocolate
indifferent individuals, even when both subjects consumed identical diets (Alcock,
Aktipis, and Maley 2014). Conflict between microbiota and host impacts satiety and
overall calorie consumption, which affects the amount of energy delivered to the gut
(Alcock, Aktipis, and Maley 2014). Energy excess is expected to reduce diversity of
microbes, which is due to certain species being able to bloom and overwhelm
inhibition by competitor organisms, and thus leading to metabolic disease and
obesity ().
Epigenetics focuses on processes that regulate how and when genes are
turned on and off, and in recent years has now become considered to be at the
epicenter of modern medicine because of its ability to explain the relationship
between individual phenotypes and the environment, and how it can relate to health
(Arkadievich 2012). It has now been proven that a variety of food ingredients and
drugs can interfere with epigenetic gene regulation (Arkadievich, 2012). Diet
nutrients of indigenous microbiota with different metabolic and signal activity can
potentially be considered to be the most significant environmental determinants
that affect gene expression in a host genome (Arkadievich 2012). A study was done

on identical agouti mice twins, the only difference between the two being the color
and size of the mice(video?). One twin was yellow and obese, while the other was
brown and lean. Both mice contain the gene agouti, but the obese yellow mouse had
the agouti gene flipped on, causing it to block a satiation receptor in the brain. The
blockage of this causes the mouse to continuously eat without feeling satisfied.
Researchers working with this strand of mice began to supplement pregnant agouti
mice food with vitamin b12, folic acid, choline, and betaine. The mothers given these
supplements gave birth to thin, brown mice. The mothers who did not receive these
supplements gave birth to obese, yellow mice with the agouti gene flipped on, which
left her babies susceptible to cancer, diabetes and other long-term diseases. The
sucestibility of these diseases being the direct cause of overeating and too much
body fat, proving that what a mother eats can change the epigenome and how genes
are expressed in her babies before they are born. (cite video)
It has been proven in many studies conducted on animals that intestinal
microbiota modulate host adiposity through different mechanisms due to diet
(Cassader, Gambino, Musso, 2012). Humans may influence their microbiota through
diet, which influences the development of obesity and other metabolic diseases
(Dibaise, Frank, Mathur, 2012). Influencing gut micrbiota should not be confused
with replacing proper diet and adequate exercise, and the differences between
intestinal microbiota between lean and obese individuals remain incompletely
understood (Dibaise, Frank, Mauthur, 2012). The best approaches to managing
human microbiota is still unknown, with the majority of studies done being unable
to generate predictive hypotheses (Alcock, Aktipis, and Maley 2014). The genetic

conflict between host and micrbiota adds a new dimension to current viewpoints
that could possibly used to explain mechanisms explaining obesity and related
metabolic diseases.

References
Alcock, J., Maley, C., & Aktipis, A. (2014). Is eating behavior manipulated by the
gastrointestinal microbiota? Evolutionary pressures and potential
mechanisms.Bioessays, 36, 940-949. Retrieved from Science Direct.
Arkadievech, B. (2012, March 28). Gut Indigenous Microbiota and Epigenetics.
Microbial Ecology in Health and Disease, 1-13.
Blaut, M., & Klaus, S. (2012). Intestinal Microbiota and Diversity. Handbook of
Experimental Pharmacology. Retrieved from Pub Med.
Dibaise, J., Frank, D., & Mathur, R. (2012). Influence of Diet on Gut Microbiota.
American Journal of Gastroenterology, 22-27. Retrieved January 1, 2014, from
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Kolata, G. (2013, September 5). Gut Bacteria From Thin Humans Can Slim Mice
Down. New York Times. Retrieved from
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