Diabetes

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The Gut-Brain Link to Depression and Obesity

It wasn’t long ago that conventional medicine debated the existence of the gut-brain axis, the connection that links your emotions, intestines and brain.

The medical community couldn’t dispute it for long, however, given that about 90 percent of serotonin, a chemical that sends messages from one side of the brain to the other, is produced in the human gut.

Obesity and diabetes are serious conditions that harm many parts of your health, including your gut. (Remember, gut health problems could be a warning sign of type 1 diabetes?)

Eating a high-fat diet, a direct contributor to obesity and diabetes, creates greater emotional problems and direct shifts in the makeup of bacteria in the gut too, according to findings from the Joslin Research Center (affiliated with Harvard Medical School).

In their work with mice, Joslin researchers had long studied the damage done by diabetes, obesity and other metabolic health problems in their work with mice fed high-fat diets.

One variable stood out in their previous research: Obese mice that had been fed high-fat diets showed far more signs of emotional problems (depression, anxiety and obsessive behaviors) than animals fed healthier diets.

For their newest study, researchers took a different approach by giving mice behavioral tests commonly used to screen drugs for depression and anxiety. They learned mice that were fed high-fat diets experienced greater amounts of depression and anxiety.

However, when scientists took steps to change the gut health makeup of obese mice by giving them antibiotics their emotional health improved.

Taking that gut bacteria shift one step further, Joslin research also discovered the gut microbiomes of obese mice triggered emotional problems when they were transplanted in germ-free mice. And other germ-free mice that received gut bacteria from obese mice given antibiotics showed no signs of emotional problems either.

Where the gut-brain link really came into play was when researchers examined parts of the brain that govern metabolism and emotions, according to Dr. C. Ronald Kahn, Chief Academic Officer who leads the Section on Integrative Physiology and Metabolism at Joslin.

Like other tissues, these areas of the brain became insulin-resistant in test animals fed high-fat diets and this resistance was mediated partly by their microbiomes, Dr. Kahn said.

The Joslin team also found alterations in the gut health of mice were linked to the production of some chemicals that send signals across the brain too.

Now, scientists are studying specific populations of bacteria involved in the gut-brain axis that may govern this process, with an eye on creating healthier metabolic profiles in the brain.

Interestingly, Dr. Kahn points out the problems of using antibiotics as “blunt tools that change many bacteria in very dramatic ways.”

“Going forward, we want to get a more sophisticated understanding about which bacteria contribute to insulin resistance in the brain and other tissues. If we could modify those bacteria, either by putting in more beneficial bacteria or reducing the number of harmful bacteria, that might be a way to see improved behavior.”

Fortunately, there’s a growing body of evidence that shows probiotics like EndoMune Advance Probiotic may be a safe and proven tool for treating behavioral issues among mice and humans and provide some extra help to fight obesity too.

Gut Health Problems May be a Sign of Type 1 Diabetes

Unlike the type 2 version, type 1 diabetes is an even more serious and virtually incurable form of the disease that prevents your body from making the insulin it needs.

What’s more, type 1 diabetes can harm the body’s major organs over the long haul, affecting the kidneys, blood vessels, nerves, heart and eyes. And, it can even make pregnancy risky for Moms and their babies.

For the longest time, medical science has assumed the origins of type 1 diabetes lie in the pancreas. The results of a recent study have led Italian researchers to look elsewhere, speculating that gut health problems may be a sign of type 1 diabetes.

“Our findings indicate the individuals with Type 1 diabetes have an inflammatory signature and microbiome that differ from what we see in people who do not have diabetes or even in those with other autoimmune conditions such as celiac disease,” says Dr. Lorenzo Piemonti of the Diabetes Research Institute at San Raffaele Hospital in Milan, Italy, according to a press release.

The pancreas or the gut?

Researchers compared samples (via biopsies of the small intestine, but not stool samples) taken from the microbiomes of 54 patients, including 19 type 1 diabetics, 16 healthy controls and 19 additional patients with celiac disease, which can damage the small intestine.

(The connection between type 1 diabetes and celiac disease is a sound one, as up to 11 percent of type 1 diabetics may suffer from celiac disease too, says Dr. Piemonti.)

Overall, patients with type 1 diabetes displayed many more signs of inflammation in the gut’s mucous membrane that were tied to 10 specific genes than those seen in healthy controls or even celiac patients, according to the study appearing in JCEM: The Journal of Clinical Endocrinology and Metabolism.

Additionally, the balance of gut bacteria in type 1 diabetes patients was distinctly different compared to the other groups.

“We don’t know if Type 1 diabetes’ signature effect on the gut is caused by or the result of the body’s own attacks on the pancreas,” Piemonti says. “By exploring this, we may be able to find new ways to treat the disease by targeting the unique gastrointestinal characteristics of individuals with Type 1 diabetes.”

Could probiotics make a difference?

Is it possible that a probiotic could make a difference one day in treating patients with type 1 diabetes?

Based on the results of a 2015 study appearing in Diabetes, Cornell University researchers had great luck with engineering a strain of Lactobacillus (gasseri) they fed to diabetic rats for 90 days.

Over that time, levels of high blood glucose fell as much as 30 percent in diabetic rates receiving this strain of beneficial probiotic bacteria. Even more promising, this probiotic bacteria reduced glucose levels in diabetic rats in the very same way as healthy animals.

Is it possible taking a probiotic with multiple strains of beneficial bacteria like EndoMune Advanced Probiotic could make a difference too?

These results may be just the start of a new way to look at and treat type 1 diabetes by rebalancing the bacteria that live in our guts.

A common diabetes drug may improve your gut health

In the past, we’ve discussed how some drugs — heartburn meds and antibiotics — harm the delicate balance of gut bacteria, making your body more vulnerable to serious health problems.

However, at least one very common drug used by type 2 diabetes patients to control their blood sugar — metformin (Fortamet and Glumetza are brand names) — may work primarily in the gut and be beneficial for gut health, based on findings of recent studies.

In the gut, not the bloodstream

Scientists at the University of North Carolina (UNC) School of Medicine discovered the connection between metformin and gut health, erasing some 60 years of assumptions that the type 2 diabetes drug worked primarily in the bloodstream, according to a Diabetes Care study.

This discovery was critical because some type 2 diabetes patients with kidney issues accumulate too much metformin in their blood, which may leave them vulnerable to other serious problems so they can’t take it.

“These findings create an opportunity to develop a new metformin treatment option for the 40 percent of patients that currently can’t take this first-line drug of choice,” says Dr. John Buse, lead author of the study and director of the Diabetes Care Center at the UNC’s School of Medicine, according to a press release.

Scientists compared the effect of three kinds of metformin — delayed-release (DR), extended-release (XR) and immediate-release (IR) — on healthy patients and those with type 2 diabetes in this two-phase study.

In phase 1 testing on 20 healthy patients, scientists found roughly half as much of the DR version of metformin in their blood compared to IR and XR forms.

Various doses of Metformin DR also performed well in phase 2 testing (comparing it to Metformin XR or a placebo in type 2 diabetes patients), as the potency of the delayed-release version increased by 40 percent.

Improved fatty acid production

A separate study conducted by European and Chinese researchers also observed the positive effects of metformin on the gut health of type 2 diabetics, even over healthy patients, featured in the journal Nature.

The gut microbiomes of type 2 diabetics from Europe and China who took metformin generated more specific kinds of beneficial short-chain fatty acids (butyric acid and propionic acid) that lowered blood sugar levels.

“We weren’t able to show that other types of anti-diabetic drugs had any actual impact on the gut microbiota,” says senior study author Dr. Olaf Borbye Petersen of the University of Copenhagen, according to a press release.

“When studying type 2 diabetes patients not being treated with metformin, we did, however, discover that they — irrespective of whether they were from Denmark, China or Sweden — had fewer of the bacteria which produce the health-promoting short-chain fatty acids.”

But, does this discovery mean the lack of fatty acid-producing bacterial species in the gut contributes to type 2 diabetes? Stay tuned for more research, says Dr. Petersen.

These findings may also explain why metformin patients experience increased flatulence and bloating, as those treated with the drug have more coliform bacteria in their gut.

Could taking a daily probiotic like EndoMune Advanced Probiotic that contains multiple strains of beneficial bacteria also make a difference in the treatment of type 2 diabetes?

Only time will tell…

Artificial sweeteners may harm your gut health

Earlier this year, we explained how poor gut health can be one underlying factor that contributes to the epidemic of obesity plaguing our country.

So, you start on the right track by getting the right amount of exercise and sleep, cutting down on fatty foods, and switching from products containing real sugar to those made with non-caloric artificial sweeteners (to liven up that early morning infusion of java).

Unfortunately, those artificial sweeteners—specifically sucralose (sold in America as Splenda), aspartame (Nutrasweet and Equal) and saccharine (Necta Sweet or Sweet‘N Low)—may have the opposite effect, according to research published in the journal Nature.

Scientists from the Weizman Institute of Science’s Department of Immunology (Israel) made the discovery after feeding 10-week-old mice one of several diets (normal or high-fat) and water laced with one of the artificial sweeteners mirroring amounts sanctioned by the FDA, plain water or water mixed with glucose.

Eleven weeks later, the test animals exhibited signs of glucose intolerance, an indicator signaling several metabolic conditions including adult-onset diabetes or metabolic syndrome. What’s more, repeating the same test with different mice and different amounts of artificial sweeteners produced the very same results.

How test animals react to artificial sweeteners

Then, researchers tested a theory that the gut’s reaction to artificial sweeteners may be triggering glucose intolerance, because our bodies don’t recognize the sugar as food, using only saccharin. Interestingly, they found saccharin isn’t absorbed by the gut but does have contact with the gut bacteria in mice, which triggers glucose intolerance.

Other signs that gut bacteria was affected by artificial sweeteners:

  • Treating the mice with antibiotics reversed the process completely.
  • Transferring the microbiota of mice harmed by artificial sweeteners to sterile mice conferred the same results to the new animals.
  • DNA sequencing revealed contact with saccharin affected the diversity of gut bacteria.
  • Even placing the affected gut microbiota outside the bodies of sterile mice along with artificial sweeteners was enough to induce glucose intolerance.

How YOUR gut reacts to artificial sweeteners

Lastly, researchers at the Weisman Institute turned to data collected from The Personalized Nutrition Project, the largest human trial to study the connections between the human gut microbiota and nutrition.

Based just on the reporting of some 400 people (at this time only from Israel) participating in the project, scientists discovered a significant connection between their gut bacteria, self-reported consumption of artificial sweeteners and clinical signs of glucose intolerance.

Finally, scientists recruited seven fit and health volunteers who didn’t use artificial sweeteners to incorporate the maximum daily amount of it in their diets for seven days. The gut health of four patients changed to a balance associated with the propensity for metabolic diseases, while the remaining three weren’t affected at all.

Why were some volunteers affected, but others weren’t? Specific bacteria in the guts of those who developed glucose intolerance reacted to the fake sugar by secreting substances that triggered an inflammatory response similar to sugar overdose, thus promoting changes in the body’s ability to metabolize sugar, said Dr. Eran Elinav.

Even more compelling: Treating mice with gut bacteria of volunteers whose gut bacteria developed glucose intolerance triggered the same result.

Taking a probiotic protects your gut

“Our relationship with our own individual mix of gut bacteria is a huge factor in determining how the food we eat affects us,” said Dr. Elinav in a press release. “Especially intriguing is the link between use of artificial sweeteners—through the bacteria in our guts—to a tendency to develop the very disorders they were designed to prevent; this calls for reassessment of today’s massive, unsupervised consumption of these substances.”

Because the effect of artificial sweeteners wasn’t universal, it’s possible that probiotics could be used to shift gut bacteria in order to reverse the damage done by glucose intolerance, said Dr. Eran Segal, Department of Computer Science and Applied Mathematics at the Weizman Institute to the New York Times.

Because your gut bacteria can change very quickly based on the good and bad foods you eat, it’s more important than ever to take a probiotic, like EndoMune Advanced Probiotic or EndoMune Advanced Junior (for kids), containing multiple strains of beneficial bacteria for your good gut health.

More And More Research Affirms The Benefits Of Healthy Bacteria

Dear EndoMune subscribers,

This month’s newsletter looks at some of the recent research on the positive effects healthy bacteria can have on the digestive system.

When I went into medicine, we spent a long time studying how bacteria caused serious infectious diseases. We learned about the importance of antibiotics and when to use them.

We never had a lecture on how certain bacteria (microflora) have co-evolved with us and how they help maintain our health.

No one really knew much about these healthy bacteria. But it turns out that they are essential for human life. We need them in our gut to digest food, synthesize certain vitamins and form a barricade against disease-causing bacteria.

But what do they look like in healthy people, and how much do they vary from person to person?

“Studies have found that the healthy bacteria can inhibit intestinal immune system from producing immune reactions against food protein lessening the risk of asthma, eczema and other allergies.”

Human Microbiome Project

The National Institute of Medicine launched the Human Microbiome Project1 (HMP) in 2008. It’s a five-year program to better understand how the bacterial communities (microbiome) that live on and in the human body protect our health.

The HMP involves 200 scientists at 80 institutions. Using the latest genetic techniques, they collect samples of bacterial genetic material from 242 healthy people.

The samples have been collected from five areas of the body: the digestive tract, the mouth, the skin, the nose and the vagina.

The projects reveal some of the ways in which invisible or microscopic bacteria shape our lives from birth to death. The ultimate goal is to test whether changes in the human microbiome are associated with human health or disease.

Benefits of a Healthy Microbiome

For example, researchers2 at Baylor College of Medicine have found that the vaginal bacterial flora or microbiomes change during pregnancy. Particular species, like Lactobacillus johnsonii, become dominant. This bacteria is usually found in the human intestinal tract where it produces enzymes that promote digestion of milk and substances that destroy harmful bacteria.

These findings have implications for the newborn. Before birth, the infant is in a sterile environment. The initial exposure to the world of bacteria is during the passage through the birth canal. It has been speculated that the baby will ingest some of the Lactobacillus johnsonii which will aid in digesting breast milk.

Babies born by Caesarean section start out with different microbiomes, but it is not yet known whether their microbiomes remain different after they mature.

During infancy, the baby’s intestinal microbiome expands and is impacted by breastfeeding. A study of 16 lactating women3 found that human breast milk had up to 600 bacterial species and resistant starches. Breast milk helps to promote the healthy intestinal bacteria which aid in digestion, immune function and protection from harmful bacteria.

Studies have found that the healthy bacteria can inhibit intestinal immune systems from producing immune reactions against food protein lessening the risk of asthma, eczema and other allergies.

Future Research Projects

In addition to the above studies, the HMP is doing research on the how the skin microbiome may play a role in skin disorders like psoriasis and eczema.

Other research projects are evaluating the intestinal microbiome in obese versus normal weight individuals. Previous studies have found that there is a difference in the bacterial flora in obese and thin animals and humans. Hopefully, the flora can be manipulated to lessen obesity and the associated disorders of diabetes, hypertension and heart disease.

The point of this newsletter is that the scientific community now recognizes the importance of maintaining a healthy microbiome. The concern is that antibiotics can upset the healthy microbiome and can contribute to chronic disorders like Crohn’s disease, ulcerative colitis and allergies.

Take Home Message

Consider taking a high quality probiotic like EndoMune to maintain a healthy microbiome balance.

Remember, EndoMune contains 10 strains of bacteria, and it is the only probiotic on the market developed by a board certified gastroenterologist.

Eat healthy, exercise and live well!!!
Best Wishes,
Dr. Hoberman

 

1) Structure, function and diversity of the healthy human microbiome. Human Microbiome Project Consortium.Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234.

2) A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. Aagaard K, Riehle K, Ma J, Segata N, Mistretta TA, Coarfa C, Raza S, Rosenbaum S, Van den Veyver I, Milosavljevic A, Gevers D, Huttenhower C, Petrosino J, Versalovic J. PLoS One. 2012;7(6):e36466. Epub 2012 Jun 13.

3) Characterization of the diversity and temporal stability of bacterial communities in human milk.Hunt KM, Foster JA, Forney LJ, Schütte UM, Beck DL, Abdo Z, Fox LK, Williams JE, McGuire MK, McGuire MA.PLoS One. 2011;6(6):e21313. Epub 2011 Jun 17.

Probiotics Shed Light on Obesity and Diabetes

Keeping up with the latest scientific developments on probiotics and human health is becoming very challenging because every month there are new and very exciting findings.

Recently, there have been several reports on how intestinal bacteria play a role in nutrition, obesity and diabetes.

Here are a few of the results of those studies:

  1. Patients who received probiotics after gastric bypass surgery lost more weight than those who received a placebo (1).
  2. Women who took probiotics starting in the first trimester of pregnancy were less likely at one year postpartum to have central or abdominal obesity as compared to the control group who did not take a probiotic (2).
  3. In a study of overweight adolescents who went on a weight loss diet, those who were successful at losing weight had a healthy change in the composition of the intestinal bacteria (3).

These and others studies in humans and animals have discovered that our intestinal bacteria affect the amount of calories we extract from the food we eat, and how we store or use those calories. The studies further suggest that obese and lean people have different intestinal bacterial flora.

Probiotics’ Regulation of Obesity and Type 2 Diabetes

There are ongoing scientific investigations aimed at determining how the gut bacteria participate in the regulation of our weight and the development of obesity and Type 2 diabetes.

In a series of experiments, it was found that mice fed a normal diet had 40% higher body fat content than germ-free mice fed a similar diet (4). The bacteria in the colon, particularly Bifidobacteria, can metabolize certain starches in our diet that we can’t digest otherwise. These extra calories harvested by the bacteria contribute to our net calorie balance. A mere 1-2% increase in calorie absorption on a daily basis can add up to many extra pounds over a year.

These studies are a little confusing. If a healthy gut flora includes Bifidobacteria, why don’t the lean individuals who have more of the Bifidobacteria gain weight?

Scientists are trying to sort out these conflicting results. To understand how the good bacteria can help control weight gain, it is important to briefly review a little biochemistry.

Whole grain foods contain starches that are resistant to digestion in the small intestines. These starches enter the colon where they are used as fuel by Bifidobacteria and Lactobacillus. The bacteria break the starches down and produce short chain fatty acids (SCFA) by a process called fermentation. The SCFA are absorbed in the colon and contribute to the calories in the diet. But the SCFA also have other effects.

One proposed mechanism is that the short chain fatty acids produced by the Bifidobacteria stimulate the release of intestinal hormones that slow the stomach emptying after a meal (5). This results in a sense of fullness or satiety with less calorie intake; it takes less to fill you up. It may be that people with the healthy bacteria who consume whole grain foods don’t eat as much.

In addition, the healthy bacteria in lean individuals suppress the proliferation of a group of bacteria called “gram negative bacteria.” Gram negative bacteria can produce a substance called lipopolysaccharide (LPS) that causes the liver to convert ingested carbohydrate calories into fat instead of burning the calories as an energy source (6). The fat is then stored in our adipose or fat tissues.

Finally, LPS has been shown to lessen our cells’ sensitivity to the insulin our pancreas produces (6). This can result in Type 2 diabetes. Studies have shown that modifying the bacterial content of the intestines can lessen the production of LPS and the potential for developing diabetes.

The evidence indicates that the gut bacteria composition can be different between healthy individuals and those who are obese and have Type 2 diabetes. The challenge is how to manipulate the intestinal bacteria to lessen these metabolic disorders.

Take home message.  Eat whole grain foods, avoid high fatty diets and consider a probiotic like EndoMune. You may just avoid weight gain and the risk of developing diabetes.

Eat healthy and live well.
Lawrence J Hoberman, MD

 

(1) Probiotics Improve Outcomes After Roux-en-Y Gastric Bypass Surgery: A Prospective Randomized Trial: Woodard G, Encarnacion B, Downey J, et al:J Gastrointest Surg. 2009 Apr 18

(2) Probiotics May Help Ward Off Obesity, Laitinen K:  Study In Pregnant Women. European Association for the Study of Obesity; Presented 2009 May 8

(3) Interplay Between Weight Loss and Gut Microbiota Composition in Overweight AdolescentsSantacruz A, Marcos A, Wärnberg J, Martí A, Martin-Matillas M, Campoy C, Moreno LA, Veiga O, Redondo-Figuero C, Garagorri JM, Azcona C, Delgado M, García-Fuentes M, Collado MC, Sanz Y. Obesity (Silver Spring). 2009 Apr 23

(4) The gut microbiota as an environmental factor that regulates fat storage. Backhed F, Ding H, Wang
T, et al. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-15723

(5)Oligofructose and long-chain inulin:influence on the gut microbial ecology of rats associated with a human faecal flora. Kleessen B, Hartmann L, Blaut M.  Br J Nutr. 2001;86(2):291-300

(6) Metabolic endotoxemia initiates obesity and insulin resistance. Cani PD, Amar J, Iglesias MA, et al
Diabetes. 2007 Jul;56(7):1761-1772. Epub 2007 Apr 24.

 

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