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The World Inside Us
continued from page 34

obese mice into normal weight mice made them heavier, and
the opposite was also true. In human studies, researches have
found that the more diverse communities of bacteria are linked to
having a normal weight, while less diverse and more homogenous
communities of bacteria are connected to being overweight and
being obese. In a recent study published in Genome Biology,
it was found that a homogenous less diverse microbiome was
associated with a higher degree of visceral fat. It remains unclear
whether changing the makeup of the microbiome will have an
effect on weight.
Diet is a major player in determining which microbes take
up residence in our guts long-term. Gut microbes may also use
their metabolic activities to influence food cravings and feelings of
satiety. The diversity of the microbiota is related to the diversity of
the diet. Younger adults trying out a wide variety of foods display
a more varied gut microbiota than adults who follow a distinct
dietary pattern. A Western diet, high in fat and refined sugars
but low in fiber, is thought to reduce microbial diversity. This can
have detrimental effects on health. The analysis of gut microbiota
patterns of rural Papua New Guineans compared with those
of people from USA showed that westernization may decrease
bacterial dispersal rates and alter the microbiota structure. The
Human hunter-gatherers Hadza of Tanzania-where people still
live outside without access to antibiotics and treated water-had
higher levels of microbial richness and biodiversity than Italian
urban controls.
A recent study published in the journal Nature investigated this
and found that when mice were fed a low-fiber diet for 4 weeks,
the levels of 60 percent of microbial species decreased significantly.
About half of these returned to normal levels when the mice
were switched back to a high-fiber diet. But even a short burst
of such an unhealthful diet left long-lasting effects, or "scars,"
on the microbial diversity, as the researchers pointed out. More
importantly, the loss of diversity became permanently established
within four generations when the mice continued to consume a
low-fiber diet.
Our intestinal microbiome has even been linked to
neuropsychologic disorders and is a key player in the gut-brain
axis. Gut bacteria produce hundreds of neurochemicals that
the brain uses to regulate basic physiological processes as well
as mental processes such as learning, memory and mood. For
example, gut bacteria manufacture about 95 percent of the body's
supply of serotonin, which influences both mood and GI activity.
In one striking example published in Gastroenterology in 2011,
Bercik and colleagues gave BALB/c mice, a strain of mice that
are typically timid and shy, a cocktail of antibiotics, dramatically
changing the composition of their gut bacteria and found that
their behavior changed profoundly, making them bold and

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adventurous. The antibiotic treatment also boosted levels of brainderived neurotrophic factor (BDNF) in the hippocampus. This
neurochemical promotes neural connections and is an important
factor in memory and mood. When the antibiotic regimen was
stopped, the animals soon reverted to their usual, cautious selves,
and their brain biochemistry also returned to normal. In a followup human study conducted at UCLA looking at healthy women,
researchers found that women who regularly consumed beneficial
bacteria known as probiotics through yogurt showed altered brain
function, and that probiotics may dampen signals that come from
the gut and go to the brain during periods of fear or anxiety. The
people in the probiotic group showed a muted response in brain
areas involved in processing and sensation, while in contrast, people
who didn't eat any yogurt had more activity in the sensory and
emotional regions of the brain.
There is also growing evidence of long term health consequences
related to increased exposure to antibiotics, because of their effects
on the gut microbiome. In an extended study looking at the link
between antibiotic use and body mass index, researchers found that
in children, the more doses of antibiotics given and the longer the
duration given, the more likely kids are to gain more weight and
retain it. It is believed that antibiotics profoundly alter the structure
of the intestinal microbiota and reduce the bacterial diversity,
specifically wiping out some populations of native flora in the gut
and replacing them with other less beneficial species that adversely
affect weight.
There has been a vast body of research studying microbial
populations in the body and their genetics; and exploring their
links to health and disease. The National Institutes of Health
(NIH) launched the Human Microbiome Project in 2007 and
aims to define the microbial species that affect humans and their
relationships to health by producing large, publicly available datasets
from genetic studies. The gut microbiota, the trillions of microbes
inhabiting the human intestine, is a complex ecological community
that through its collective metabolic activities and host interactions,
influences both normal physiology and disease susceptibilities.
Understanding factors underlying compositional and functional
changes of these populations living in our digestive tract will aid
in designing disease-eradicating therapies that target our gut flora.
While there remain many unanswered questions, the gut microbiota
is truly becoming a cornerstone of preventive medicine.
References
Beaumont M, , Goodrich JK, Jackson MA, Yet I, Davenport ER, et
al. (2016). Heritable components of the human fecal microbiome are
associated with visceral fat. Genome Biology. 17:189.
Bercik P, Denou E, Collins J, Jackson W, Lu J, et al. (2011).
The Intestinal Microbiota Affect Central Levels of Brain-Derived
Neurotropic Factor and Behavior in Mice. Gastroenterology. 141:599609.


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Berks County Medical Society Medical Record Fall 2018

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