World War You

World War You

by Guest Blogger,
Tyler Kokjohn, Ph.D.

WWY2The 20th century began a period of notable public health improvements in which average life expectancy increased from just under 49 years to nearly 79 years today (1, 2).  A combination of factors including vaccines, improved living conditions and antimicrobial drug therapies decreased the threat of early death from many infectious diseases (3).  Today death is often the long term consequence of chronic conditions such as heart (cardiovascular system) disease, cancer and diabetes.

Antibiotics vanquished a number of bacterial diseases and for a while they certainly looked like miracle cures.  However, while battles with infectious diseases were being won, a sign of serious trouble, drug resistance, emerged quickly.  For a while steady development of new antibiotics enabled physicians to keep pace.  Eventually, rising tides of resistance forced the medical community to acknowledge the miracle of antibiotic resistance might be squandered (3).  Medical professionals were called on to use antibiotics judiciously and follow procedures to reduce the spread of drug-resistant microbes – more than 25 years ago.  The longstanding problems have never been resolved and some are much deeper than we first imagined.

Antibiotics are often so effective at killing or suppressing it once appeared our microbial enemies were doomed.  However, our petri dish models were limited and led us to underestimate the adaptive potential of bacteria.  Microbes have been fighting each other with antibiotics for a long time and some had developed effective mechanisms to inactivate or eliminate them.  In addition, many antibiotic resistance factors are on DNA elements that can be passed to other bacteria.  What this means is that the bacterial pathogens we seek to destroy not only have access to pre-evolved antibiotic resistance genes and they are also adept at genetic plagiarism.  Once one of them acquires the right genes, ruthless selection coupled with fast transfers enables rampant antibiotic resistance spread.

We have been slow to recognize that the human body is a complex and dynamic ecosystem.  Our external and many internal surfaces are populated with thousands of different microbial species.  We and our billions of tiny companions are mutually interdependent to a degree that is only now beginning to be understood (4).  Physicians may prescribe an antibiotic to destroy a specific pathogen, but sensitive bacteria that happen to be in the neighborhood will be decimated along with the target.  Antibiotic treatments may eliminate the pathogen but they also change the composition of our normal microbial flora (5).  Hopefully, any disturbances are minor and temporary, but antibiotic treatment-induced alterations in gastrointestinal microbial community composition sometimes become catastrophic for the patient.  Antibiotics and anti-cancer treatments that disrupt the normal microbial balance in the colon may create a situation in which overgrowth of the bacterium Clostridium difficile produces serious, sometimes fatal disease (6).  Induced by medical treatment, the best hope for recovery from a disease produced by one antibiotic has been to switch to a different antibiotic and pray the patient improved.  This strategy often failed and a promising new approach has been to reconstitute the normal bacterial population using fecal transplants from healthy donors (6).

FireWe have been tossing powerful drugs into complex, interactive communities with little understanding of their potential downstream ecological consequences.  Tunnel vision and a lack of appreciation for interconnections between networks have been a traditional feature of ecosystem management by humans.  Our medical approaches have been successful, but several shortcomings are coming back to haunt us.

Modern animal husbandry practices provide enormous quantities of affordable foods.  They also increase the threat of human disease (7).  Actions taken to address economic concerns and consumer preferences may end up having important public health implications.  How animals are fed, housed, handled and transported to slaughter may favor the emergence and proliferation of highly pathogenic agents like enterohemorrhagic E. coli O157:H7.  Feeding corn to cattle in order to increase production efficiency promotes colonization with E. coli O157:H7 (8) and stress may enhance the growth of these pathogens (9) in herd animals held in crowded feedlots.

Using antibiotics on food animals may directly select populations of drug-resistant bacteria which might go on to infect humans (7).  Worries about fostering the transfer of nasty pathogens seem well founded; millions of instances of food poisoning are caused each year by bacteria that get from our food animals into us.  One strategy suggested to mitigate the threat is ensuring antibiotics currently important in the treatment of human infections are employed only under carefully regulated situations in animal husbandry (7).

Nearly 70 years ago researchers discovered that herd and flock animals fed antibiotics gained weight (10).  Estimates of the amounts of antibiotics now being provided to enhance the growth of healthy animals vary (11), but it is clear the totals are substantial.  The exact reason(s) behind the growth enhancement phenomenon is unclear, but it is probable the normal dynamics of gut ecology – the interplay between animal hosts, their food and the microbial populations living within them – are fundamentally altered by sub-therapeutic antibiotic treatments.  We have only vague ideas as to the species composing the microbial worlds within our food animals and even less certain concepts about how they respond to antibiotic exposures.

If antibiotic feeding promotes growth in food animals, what are the human health implications?  One fact is clear; persons fed antibiotics gain weight just like farm animals (10).  Some scientists suspect the intermittent exposures to prescription antibiotics many of us experience are sufficient to disrupt the normal ecological balance of our digestive systems.  If this idea is correct, antibiotic treatments may be contributing directly to an increasing incidence of obesity and other conditions such as diabetes and allergies (5).  Some compelling results supporting this hypothesis are in hand, but antibiotic exposure is one of many factors, including diet, that could be altering our normal populations of gut microbes (12).

The war against infectious diseases has been a monumental success.  However, from the microbial ecology perspective some antibiotic treatments are a scorched earth approach with global impacts.  Understanding the worlds within us may lead to new strategies to prevent or cure disease without inflicting so much collateral damage on our mostly peaceful microbial partners.  All of us have a stake in the outcome of World War You.
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(1)   D. Leonhardt.  2006.  Life Expectancy Data.  The New York Times, September 27, 2006.  http://www.nytimes.com/2006/09/27/business/27leonhardt_sidebar.html

(2)   E. Arias.  2011.  National Vital Statistics Report, Volume 64, Number 11, September 22, 2015. http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_11.pdf

(3)   M. L. Cohen.  1992.  Epidemiology of Drug Resistance: Implications for a Post-Antimicrobial Era. Science 257:1050-1055.

(4)   J. E. Brody.  2014.  We Are Our Bacteria.  The New York Times, 14 July 2014. http://well.blogs.nytimes.com/2014/07/14/we-are-our-bacteria/?_r=0

(5)   M. J. Blaser.  2016.  Antibiotic Use and Its Consequences for the Normal Microbiome.  Science352:544-545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939477/

(6)   P. A. Smith.  2015.  Fecal Transplants Made (Somewhat) More Palatable.  The New York Times, 9 November 2015. http://www.nytimes.com/2015/11/10/health/fecal-transplants-made-somewhat-more-palatable.html

(7)   Antibiotic Use in Food-Producing Animals.  National Antimicrobial Resistance Monitoring System for enteric Bacteria, Centers for Disease Control and Resistance.  http://www.cdc.gov/narms/animals.html

(8)   T. R. Callaway et al.  2009.  Diet, Escherichia coli O157:H7 and Cattle: A Review After 10 Years.Current Issues in Molecular Biology 11:67-80. http://www.horizonpress.com/cimb/v/v11/67.pdf

(9)   L. Galland.  2014.  The Gut Microbiome and the Brain.  Journal of Medicinal Food 17(12):1261-1272. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259177/

(10)  P. Kennedy. The Fat Drug.  The New York Times, 8 March 2014.  http://www.nytimes.com/2014/03/09/opinion/sunday/the-fat-drug.html

(11)  T. F. Landers et al.  2012. A Review of Antibiotic Use in Food Animals: Perspective, Policy and Potential.  Public Health Reports 127(1):4-22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234384/

(12)  T. Kokjohn.  2016.  Food for Thought? https://jayvay.wordpress.com/2016/08/24/food-for-thought/

 

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Food for Thought?

Food for Thought?

by Guest Blogger,
Tyler Kokjohn, Ph.D.

 Veslius CNS and PNSOur gastrointestinal (GI) tracts are home to billions of microbes.  Microbiologists have known for a long time our guts are well colonized, but the full complexity and importance of the GI microbiome was recognized only recently.  Around 1,000 different bacterial species may reside in this part of our bodies during the course of our lives (1).

The microbial universe hidden within us exerts major impacts on our physiology, development and perhaps much more (1,2).  Gut microbes produce neurotransmitters (1) which may influence diverse activities such as cognitive function, social interactions and adaptive responses to stress (1,3,4).  However, communications flow in both directions.  The brain is hardwired into the GI tract directly by the vagus nerve and may modulate microbial activities through several mechanisms (4,5,6).  Animal studies have shown that the composition and metabolic activities of the gut microbiome are sensitive to stress (5) and disrupting it may produce serious consequences.

Aging and low fiber diets impoverish the gut microbiome (7,8).  These observations invite speculation that modern day eating habits are promoting a broad range of pathologic conditions including age-related frailty (7).  It literally gets worse – experiments with rodents suggest gut microbiome diversity may drop with each new generation (8).  Perhaps our diets have accidentally driven the microbial symbionts essential for robust health to extinction and hastened the onset of maladies such as Alzheimer’s disease (AD) or worsened their impacts (9).

Although to this point most of the experiments manipulating GI microbiomes have been conducted in rodents, the implications for human health could clearly be staggering (10).  We share our microbial passengers with others through casual contact, could some conditions regarded as purely mental (brain) diseases actually be contagious?  Persons who maintain social interactions in old age seem more likely to avoid AD.  Maybe the long noted cognitive benefits of social engagement are partially due to periodic re-inoculation with essential bacteria that would otherwise be lost with aging and physical isolation.  The GI microbiome is dynamic and perhaps one day physicians will maintain and promote mental wellbeing by prescribing ‘psychobiotics’- probiotic microbe-containing supplements analogous to foods like yogurts (10, 11).

GI microbiome research is currently in the unbounded optimism phase.  Fecal transplants are being used to help patients recover from severe Clostridium difficile infections of the GI tract (12).  OpenBiome, a non-profit organization, now distributes healthy donor fecal samples in pill form to facilitate treatment and research.  Undoubtedly amazing new insights and some novel approaches to improve human health are in the offing.  Although companies are moving ahead quickly (11) scientists are attempting to manipulate still largely unexplored living ecosystems and not every good idea is sure to become a miracle cure.   The efforts to eradicate C. difficile infections provide an instructive example.  While fecal transplants have produced remarkable benefits, how they work is still unknown and recent clinical trials of similar strategies have produced disappointing outcomes (13).  Medical issues like obesity and AD are equally or more complex and it seems likely that improved diets and probiotics will be only one facet of correspondingly complicated future management strategies.

OpenBiome

www.openbiome.org

Why we’re here. We founded OpenBiome, a nonprofit 501(c)(3) organization, after watching a friend and family member suffer through 18 months of C. difficile and 7 …

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(1)   T. G. Dinan et al.  2015.  Collective Unconscious: How Gut Microbes Shape Human Behavior.  Journal of Psychiatric Research 63:1-9.    http://www.sciencedirect.com/science/article/pii/S0022395615000655
(2)   E. P. J. G. Neis et al.  2015.  The Role of Microbial Amino Acid Metabolism in Host Metabolism. Nutrients 7:2930-2946.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425181/
(3)   P. A. Smith.  2015.  The Tantalizing Links Between Gut Microbes and the Brain.  Nature 14 October 2015, (526:312-314).  http://www.nature.com/news/the-tantalizing-links-between-gut-microbes-and-the-brain-1.18557
(4)   S. Reardon.  2014.  Gut-brain Link Grabs Neuroscientists. Nature, 12 November 2014, (515:175-177).   http://www.nature.com/news/gut-brain-link-grabs-neuroscientists-1.16316
(5)   E. A. Mayer et al.  2014.  Gut Microbes and the Brain: Paradigm Shift in Neuroscience.  The Journal of Neuroscience 34(46):15490-15496.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228144/
(6)   C. Schmidt.  2015.  Thinking From the Gut.  Nature, 25 February 2015, (518:S12-S15). http://www.nature.com/nature/journal/v518/n7540_supp/full/518S13a.html
(7)   P. W. O’Toole and I. B. Jeffery.  2015.  Gut Microbiota and Aging.  Science 350:1214-1215.  http://science.sciencemag.org/content/350/6265/1214
(8)   K. H. Courage.  2016.  Your Poor Diet Might Hurt Your Grandchildren’s Guts.  Science 13 January 2016.  http://www.sciencemag.org/news/2016/01/your-poor-diet-might-hurt-your-grandchildren-s-guts
(9)   S. Bhattacharjee and W. J. Lukiw.  2013.  Alzheimer’s Disease and the Microbiome.  Frontiers in Cellular Neuroscience 7:153.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775450/
(10)  L. Sanders.  2016.  Microbes Can Play Games with the Mind.  Science News, 23 March 2016.  https://www.sciencenews.org/article/microbes-can-play-games-mind
(11)   S. Reardon.  Microbiome Therapy Gains Market Traction.  Nature, 13 May 2014, (509:269-270).  http://www.nature.com/news/microbiome-therapy-gains-market-traction-1.15210
(12)   P. A. Smith.  2015.  Fecal Transplants Made (Somewhat) More Palatable.  The New York Times, 9 November 2015.  http://www.nytimes.com/2015/11/10/health/fecal-transplants-made-somewhat-more-palatable.html?_r=0
(13)   R. Cross.  2016.  Poop Pill’s Surprising Failure Shows that the Microbiome is Still a Mystery. MIT Technology Review, 29 July 2016.  https://www.technologyreview.com/s/602044/poop-pills-surprise-failure-shows-that-the-microbiome-is-still-a-mystery/

 

 

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The Soundtrack of Living Mystery

Jaylon Productions, LLC

Living Mystery Poster

Aloha, Everyone. Just want to take a moment to thank Joe Gooch for producing two songs for the Living Mystery Symposium. Joe was instrumental (literally and figuratively) in adding to the ever-evolving Paratopia soundtrack over the years and created the theme song to The Experience. He is an endless creative force and a friend. Although he cannot make the symposium this year, he’ll be here in spirit and in song. Check them out!

awakening – by Joe Gooch
https://soundcloud.com/paranormalmusic/a-w-a-k-e-n-i-n-g-by-joe-gooch

Living In The Mystery – by Joe Gooch
https://soundcloud.com/paranormalmusic2/living-in-the-mystery-by-joe-gooch

Mahalo, Joe!

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