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From the Townsend Letter
June 2017

Anti-Aging Medicine
Anti-Aging Guide to Maintaining a Healthy Gut Microbiome
by Ronald Klatz, MD, DO,
and Robert Goldman, MD, PhD, DO, FAASP

www.worldhealth.net
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The gastrointestinal tract contains the largest amount and concentration of microbes found in the human body. Changes occurring in the gut microbiome during aging can have a negative impact on health and contain a high degree of variability. A major controllable factor that influences the composition of the microbiome is diet. The nutritional value of food is determined in part by the gut microbial community, or microbiota, and its component genes (microbiome). Switching from a low-fat, plant-rich diet to one containing high-fat and high-sugar (otherwise known as the "Western" diet) changes the structure of the microbiota within 24 hours, altering the representation of metabolic pathways and the genes in the microbiome. In this column, we review recent studies that suggest natural methods of maintaining a healthy digestive system.

Turnbaugh PJ, et al. The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice, Sci Transl Med. 11 Nov 2009;1(6).

Abx SupportGut Microbes, Diet, and Host Gene Expression
New research has found that changes in diet affect our gut microbe population and our health. More evidence has shown the important role bacteria plays in our gut and how they alter gene expression depending on diet preferences. Researchers discovered that Western diets, poor in fiber-rich whole plant food, do not provide nourishment for the microbes. The number of microbes in our guts can reach in the trillions and weigh as much as 2 kilograms (4 or 5 pounds). Through fermentation, they help to digest food and produce compounds called metabolites that help the immune system and act as a barrier to infections. The report was published in the journal Molecular Cell by a team of researchers from the University of Wisconsin-Madison.
     
Genes in our DNA make up the code that makes life possible. However, genes can be altered by many environmental factors that switch some genes on or off. The complete set of genes that make up our entire DNA is called the genome, and molecules called epigenome communicate with the genome.
     
In the study, the researchers found small levels of molecules that were communicating with cells of the mice through the epigenome. UW-Madison professor John M. Denu suggests that metabolites (compounds created by gut microbes) and possibly many other compounds were communicating with the epigenome.
     
The researchers used lab mice in two groups with different diets. One group was fed plant food high in carbohydrates to mimic a human diet rich in fiber, and the other group was fed a diet of sugar and fat to mimic a typical Western diet. The team then compared the mice fed the Western-style diet to those fed the plant-food diet and discovered the Western diet deterred many epigenetic changes that occur naturally with the plant diet. The researchers then supplemented the diet of the mice that were fed fats and sugars with metabolites. This supplementation restored the proper epigenetic changes seen in the group of mice fed plant food.

Professor Denu and his colleagues suggest the study helped to prove that metabolites that are produced by microbes in the gut when fed a plant-based diet are the major communicators to the epigenome. They call the microbe functions "microbial metabolism." It turns out that food rich in sugar or fat are easily digested but are not a good source of nutrients for the gut bacteria. When the microbes are starved under this diet, the result is a less diverse microbiome with poorer communication with the epigenome.
     
A surprising result of the study was the discovery that these complex communications in the gut microbiome are not confined to the colon but also between liver cells and fatty tissue inside the gut. This study has profound implications for future studies of the complex interactions between different diets and a healthy gut microbiota.
     
Scientists are beginning to understand the mechanisms of the bacteria in the microbiome. This study has revealed that gut microbes that are fed a fiber-rich diet of fruits and vegetables produce metabolites that can positively affect our health. But the underlying mechanisms are still poorly understood, and further research in this area could give scientists the tools to create microbiota supplements. This would be a breakthrough for people who eat a Western-style diet because microbes in the gut help digest excess food thus helping to maintain a healthy weight.

Krautkramer KA, et al. Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues. Molecular Cell, doi:10.1016/j.molcel.2016.10.025, published online 23 November 2016.

Pineapples Halt Harmful Gut Bacteria
Scientists working to find new ways to treat antibiotic-resistant superbugs have discovered a possibility in the stems and roots of pineapples. A group of three enzymes known as bromelain were initially discovered in the 1930s, but the uncovering of their antibiotic qualities happened only a few decades ago, with Australian scientists now using the enzymes to cure diarrhea in piglets. While antibiotics target bacteria, bromelain works with the cells in the gut by making it difficult for the bacteria to stick to the cells. The chance of bacteria evolving and becoming resistant is limited by the three enzymes targeting gut cells. According to Rob Pike, a biochemist from LaTrobe University located in Melbourne, Australia, since pigs and humans are anatomically and physiologically similar in several ways, the enzymes have the potential to provide an alternative treatment for people. Scientists hope this will be the case in humans, so diarrhea will not occur.
     
It is crucial to find alternative treatments for superbugs because they are predicted to kill about 10 million people a year by 2050, more than the number of people killed by cancer. Scientists hope the new enzymes from pineapple can be used as another weapon to fight bacteria, as many antibiotics do not work as well as they used to. "The momentum to develop alternatives to antibiotics is there now because people believe antibiotics are on the way out and we need something to replace them," said Pike.
     
Professor Pike and his colleague Lakshmi Wijeyewickrema are presently developing the alternative treatment to antibiotics along with Anatara Life Science, which also conducted the animal trials.

Palmer D. Pineapples Can Stop Harmful Bacteria in the Gut. Parent Herald. June 27, 2016.
Smith B. Pineapples could play key role in global superbug battle. Sydney Morning Herald. June 23, 2016.

CoreBioticAgave Extracts Help Improve GI Health
Prebiotics are digestion-resistant compounds that feed the "good bacteria" in the GI tract.  The agave plant contains inulin, a polysaccharide for which some previous studies suggest a physiologic effect.  Kelly Swanson, from the University of Illinois (Illinois, USA), and colleagues enrolled 29 healthy adults in a three-period crossover double-blind study in which subjects were randomized to one of three groups: 0, 5.0, or 7.5 grams per day of agave inulin. Each period was followed by a seven-day washout before crossover. Fecal samples were collected and fermented, then analyzed to determine gut bacteria populations.  Data analysis revealed that Bifidobacterium levels increased four-fold after 5.0 and 7.5 grams per day agave inulin, and Desultivibrio (anaerobic sulfate-reducing bacteria) levels decreased 40%. Agave inulin consumption was also associated with reduced fecal pH and increased butyrate – suggesting increased saccharolytic fermentation and reduced proteolytic fermentation. The study authors observe, "Agave inulin supplementation shifted the gastrointestinal microbiota composition and activity in healthy adults."

Holscher HD, et al.  Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.  J Nutr. 2015 Jul 22. pii: jn217331.

A Pair of Benefits of Pears
A fruit of the Rosacie family of trees, the pear is abundant in antioxidants, flavonoids, and dietary fiber while being fat- and cholesterol-free and low in calories. Dipayan Sarkar, from the University of Massachusetts (Massachusetts, USA), and colleagues analyzed the pulp and skin of the Bartlett and Starkrimson varieties of pear to ascertain the probiotic potential of the compounds present in the fruit.  The researchers found that the peel (as compared to pulp) of the pear exhibited a high phenolic content; whereas the pulp was high in antioxidant activity. As well, the team observed that fermented whole pear juice exerted an inhibitory effect on the stomach ulcer bacterium, Helicobacter pylori. Observing that "[p]ear has potential for phenolic-linked management of type 2 diabetes associated hyperglycemia and hypertension," the study authors submit, "This in vitro study provides conceptual foundation for animal and clinical studies involving pear to combat type 2 diabetes."

Sarkar D, et al. Dietary functional benefits of Bartlett and Starkrimson pears for potential management of hyperglycemia, hypertension and ulcer bacteria Helicobacter pylori while supporting beneficial probiotic bacterial response. Food Research International. March 2015;69:80-90.

Gut Bacteria Linked to Age-Related Diseases
New research suggests that treating a leaky gut may promote longevity. Alterations in the intestinal microbiota have been linked with aging and measures of frailty in the elderly. To investigate this, Dr Rebecca Clark, a UCLA postdoctoral scholar when the research was conducted and now a lecturer at Durham University (England), and colleagues analyzed the gut bacteria of more than 10,000 female fruit flies, to see if their microbiota had any impact upon lifespan. Previous research by the same group had revealed that fruit flies develop a leaky gut five or six days before they die. Study results showed that the scientists were able to detect changes in the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, which occurred just prior to the development of leaky gut. The researchers then went on to show that it is possible to reduce bacterial levels in the intestine and prevent the flies from developing leaky gut by treating them with antibiotics. Results also revealed that using antibiotics to reduce bacterial levels can significantly prolong the flies' lifespan. Flies treated with antibiotics as soon as changes in their microbiota were detected lived for an average of 20 days, whereas untreated flies with leaky intestines died within a week. "The health of the intestine – in particular the maintenance of the barrier protecting the rest of the body from the contents of the gut – is very important and might break down with aging," said Dr. Clark.

Clark RI, et al. Distinct shifts in microbiota composition during drosophila aging impair intestinal function and drive mortality. Cell Rep. 2015;12:1656-1667.

To stay updated on the latest breakthroughs in natural approaches to maintain a healthy gut microbiome, visit the World Health Network (www.worldhealth.net), the official educational website of the A4M and your one-stop resource for authoritative anti-aging information. Be sure to sign up for the free Longevity Magazine e-journal, your weekly health newsletter featuring wellness, prevention, and biotech advancements in longevity.

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