Microbiome, Metabolome & Disease


 

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Many of us have followed the research in this field for health, happiness and well-being. Today’s questions and answers from an expert on microbiota in Reddit Science is of great interest and something I wanted on these pages for future reference. I sifted through the pages to condense the questions, leaving answers intact. AMA is short for Ask Me Anything. Where Professor Barrett’s  responses to questions are clear, I have omitted the questions; where not clear, questions are abbreviated and/or added. I am sure we would all like much more information on inflammation and the inflammasome, the gut and brain and health. Support science. Be careful of low quality journals and quackery. She says even some yogurts have no bacteria.

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Science AMA Series: I’m Kim Barrett, Professor of Medicine at the University of California, San Diego and Editor of The Journal of Physiology. This week, we published an issue on the microbiota [editorial free], so I thought it would be a great opportunity to discuss how our microbes influence our well being. AMA!

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This is her main message, again and again:

[–]Kim_Barrett

Eat a well-balanced diet, including cultured/fermented foods, and avoid excessive fat and processed carbohydrates..

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[–]Kim_Barrett

Thanks to both. There is a lot of epidemiological evidence for the health benefits of all of these fermented foods, which may deliver bacteria similar to probiotics as well as beneficial metabolites that have greater bioavailabilty. These foods have been consumed by humans for millennia but were less prevalent in the diet as society discovered refrigeration etc. But studies to actually prove efficacy and mechanisms of action remain in their infancy. This is an area where the National Center for Complementary and Integrative Health is placing a lot of emphasis for research funding.

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Q Nose/sinuses:

[–]Kim_Barrett

Yes, this is a less appreciated area but rapidly growing area of study. I definitely would encourage you to look at our special issue of the Journal of Physiology, which has short reviews on the oral, skin and vaginal microbiota. Our external cavities all have their own distinctive microbiotas, but in aggregate they may encode many of the same sorts of metabolic capacities as seen in the gut. The specific populations may also depend on the type of environment – for example, the bugs on your forearm are different from those on your forehead. Lots more work to be done.

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there is not a simple way currently of knowing about our microbiota’s composition, but general indices of gut health may give some clues. Likewise, finding effective probiotics may be a bit of a case of trial-and-error, but there is good epidemiological evidence for a beneficial effect of fermented foods like Kombucha.

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Q on IBS:

[–]Kim_Barrett 

Serotonin is a major controller of gut motility and sensation, and alterations in serotonin signaling have been documented in irritable bowel syndrome. The cells that make serotonin in the gut have been shown to express receptors for short chain fatty acids (SCFAs), which are major products of bacterial metabolism of undigested carbohydrates. Finally, some gut bacteria metabolize the serotonin precursoe, tryptophan, which in turn has implications for the production of appropriate gut levels of serotonin.

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Q:  Sometimes, when I am constipated, I can perceive a certain taste and smell that arrives internally. Have direct nerve connections between the bowel and the brain been identified? What role to microbiota play in perception of satiety? What is the importance of the neurological phenomenon vs the blood chemistry in controlling weight gain or loss?

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[–]Kim_Barrett 

Lots of nerve connections between the brain and gut, and gut nerve endings have been shown to sense bacterial metabolites. To the extent that the microbiota and their metabolites control the secretion of GI hormones, they clearly participate in satiety perception, but this still needs further study. And weight gain/loss is such a complex phenomenon, also encompassing societal and behavioral aspects, that the relative contributions of the factors you mention have not been worked out by any means.

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Good and bad may be too simplistic. A “good” bacteria may be bad for you if in the wrong place. As for substrates and products, this is probably too big of a topic to tackle right now, but I would direct you to the work of Eugene Chang at the University of Chicago who has done a lot of work in this area. Gut permeability is also clearly important. We have done work to show that certain commensal and probiotic species can tighten the gut barrier so that pathogens and toxic metabolites are less able to penetrate and initiate inappropriate inflammatory reactions and a vicious cycle of further weakening of the gut barrier.

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Q   Strong evidence correlates aberrations in gut diversity with certain diseases. Phylogentitcally speaking, it seems to matter more that the microbiome is diverse and less important which species are specifically there. The hypothesis being that the gut microbial metabolome is relatively stable, regardless of specific species present. http://go.nature.com/2iQLOu1

Q1 – Have clinicians started to take the next step, looking at disease correlations with perturbation of the microbial metabolome?

Q2 – If so, what have they found? Do probiotics replace those missing metabolic pathways?

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[–]Kim_Barrett 

Absolutely agree with your comments about the metabolome. However, most of this work at present is still in preclinical models, although there has been a lot of attention to the way in which metabolic pathways change after bariatric surgery, for example.

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Q:

When I was very young, I had a few instances of food poisoning visiting family in Mexico, I even contacted tuberculosis. I, of course, was given many antibiotics. I’ve had a lot of digestive issues since then, it was always a problem. I’m 36 now, and adopted a very low carb diet 3 years ago. During the initial transition, I had, to put it succinctly, severe dhiarrea. Like stuff was probably dieing off. And then, 4 months in, I had more energy, metal alertness, and general feeling of being present. And I no longer had crippling depression. From a completely anecdotal standpoint, I think that changing my diet also drastically changed my gut biome, and that, in turn, actually effected my brain function. It seems like what you’re research has shown is that this isn’t some woo-woo thinking, but an actual thing?

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Q does Kefir boost gut bacteria?

[–]Kim_Barrett

Yes, along with other related foods.

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Q are we discovering new categories of bacteria in the body?

[–]Kim_Barrett 

This was a big sticking point in the field initially since many of the bacteria cannot be cultured. Now they are identified by sequencing. The estimate is that healthy individuals harbor at least 1000 different species. Not to mention viruses, fungi, protea….we’re just getting started, and as you imply, the bioinformatics challenges are huge.

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[–]Kim_Barrett 

There’s quite a bit of evidence that mixtures of different bacteria are more effective than single bacteria. Perhaps they have complementary metabolic functions, or mutually help each other to colonize the gut.

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Q  research of healthy bacteria for auto immune disease?  Crohn’s disease?

[–]Kim_Barrett

Others are exploring a role in asthma.

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Q: studies in which obese mice had received gut flora from lean mice and subsequently lost weight, and vice versa. Does this imply that a microbial treatment for obesity in humans could be developed, and if so, is there any interest in this?

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[–]Kim_Barrett 

A lot of people are looking for just such a treatment!

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Caffeine May Reduce Age-Related Inflammation, Stanford Aging Study


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Caffeine may be able to reduce inflammation.

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Inflammatory immune molecules increase as we age and are associated with mortality from all causes, Alzheimer’s disease, stiffening of arteries, hypertension and cardiac disease. Inflammation kills. Yesterday Stanford and colleagues from University of Bordeaux published results of a long term aging study of 114 patients in Nature Medicine (paywall):

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Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

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For nonscientists, see below. Caffeine may block inflammation. Adenosine and adenine are known to stimulate the inflammasome. Caffeine blocks the effect of adenosine.

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“They found that older people between the ages of 60 and 89 tend to ramp up production of immune molecules in a complex called the inflammasome. That’s a clump of immune proteins inside cells that activate one of the immune system’s big guns, called interleukin 1 beta or IL-1B. It’s an important molecule for fighting off infection, but too much of it for too long has been linked with chronic diseases like heart diseasecancer, and Alzheimer’s disease.

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Among the older people in the study, 12 of them made much more of these inflammatory molecules, and 11 people made much less. The less-inflamed group was also healthier, with lower blood pressure, more flexible arteries, and more relatives who lived past age 90.

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They also had lower levels of the breakdown products of DNA and RNA circulating in their blood, including one molecule called adenine, and another called adenosine — which is adenine attached to a sugar molecule. These molecules are known to stimulate the inflammasome, and lower levels of them could explain why this group was less inflamed. In fact, treating cells with these breakdown products made them churn out more inflammatory molecules, and made mice more inflamed, with higher blood pressure.

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HIGHER BLOOD LEVELS OF CAFFEINE CORRELATED WITH LESS INFLAMMATION

That’s where the caffeine comes in. Caffeine is known to block the effects of adenosine in the brain — that’s how scientists think it keeps us awake. So, the researchers suspected that it’s possible that it could block the effects of adenine and adenosine on immune cells, too, and reduce their ability to cause inflammation. According to a questionnaire, people in the less inflamed group consumed more caffeinated beverages like coffee, soda, and tea. In fact, higher blood levels of caffeine and other caffeine breakdown products correlated with lower production of inflammatory molecules like IL-1B.

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When the scientists treated cells with adenine and another molecule known to trigger the inflammasome, the cells that were soaking in caffeine produced far lower levels of inflammatory molecules. The researchers still haven’t fully explained how caffeine is interfering with inflammation. And the results aren’t enough to base any behavioral recommendations off of; but it’s comforting news for those of us who were already reaching for that second hit of caffeine, anyways.”

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Many articles on pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are found in the setting of chronic pain and in depression:

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IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress.

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Depressed rodents shown to have inflammation, published by Yale and NIMH a few years ago.

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The material on this site is for informational purposes only.
.
It is not legal for me to provide medical advice without an examination.

.
It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~~
This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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