Charles Darwin

"The love for all living creatures is the most noble attribute of man." Charles Darwin

Sunday, January 10, 2016

The Gut Microbiome










So there was this one time when I had cause to be in the hospital for a few days on a course of intravenous antibiotics. This was followed by a lengthy recovery period at home, where every few days I was attended to by a member of a travelling band of angelic nurses, who came to clean and change my dressings.

As is my nature, I would always answer their questions of, "Is everything okay? ... Any problems we should be aware of? ... etc. with a, "All good, no complaints here." 

At least that was the case until one day, when the problem I was uncomfortable broaching made its way from my drug infused brain to my drug infused tongue. It went something like, "Well, there is perhaps the slight discomfort of the molten lava coming out of my bottom."

"You mean you haven't had a solid movement?"
"Not even close."
"Did the doctors not tell you that you should be taking probiotics?"
"Probi-what?"
"With the amount of antibiotics you were given, you're likely to have wiped out your good gut flora."
"My good gut what?"

Long story short, the brilliant and skilled surgeons may have saved my life and limb but that nurse, I credit her with saving my GI tract.



THE HUMAN MICROBIOME

The human microbiome is defined as the collective genomes of the microorganisms that live inside and on the human body. [National Human Genome Research Institute

Contrary to reports, our bodies do not contain 10 to 100 times more bacteria cells than human cells. The ratio is likely to be more in the neighborhood of 1.3:1. [sciencealert.com]

The roughly 100 trillion bacteria and other microbes which comprise the microbiome [1] account for approximately 1-3% of our total body mass. [2]

The human body emits bacteria into the air to create a microbial cloud around the body, which may be used to uniquely identify a person. [3-4]

By genetically mapping the microbiome of 242 healthy individuals, researchers with the Human Microbiome Project (HMP) calculated that more than 10,000 microbial species occupy the human ecosystem. [3][5]

Though species vary widely between individuals, they stay fairly constant within an individual over time; although some alterations may occur with changes in lifestyle, diet, age [6], and immune status. [7]

Analyzing the effects of kinship on the microbiome across countries, it has been found that sharing numerous common environmental exposures in a family is a strong determinant of individual microbiome composition. This effect has no genetic influence and it is consistently observed in culturally different populations. [8]

What follows focuses in on the gut microbiome/microbiotia specifically. 



THE GUT MICROBIOME

The gut microbiome refers to the collective genomes of gut bacteria. 

Gut microbiota (gut flora), consists of a complex community of microorganisms that live in the digestive tracts of animals. [9]





Gastrointestinal Tract



Escherichia coli, one of the many species of 
bacteria present in the human gut [9]



Functions of gut microbiota (flora)

Beneficial gut flora repress the growth of harmful gut flora through competitive exclusion. This protects humans from both invading species and species normally present in the gut in low numbers. [12-14]



C. difficile colonies on a blood agar plate. 
The overgrowth of C. difficile in the gut can be 
harmful to the host. [9]



  • Gut flora play a critical role in digestion by breaking down plant fiber. [15]
  • They turn the carbohydrates they ferment into materials which can be used by host cells to provide energy and nutrients. [16]
  • They help the body to absorb essential dietary minerals such as calcium, magnesium and iron. [12]
  • They help control how we store fat, how we balance levels of glucose in our bloodstream and how we respond to hormones that regulate hunger. [15]
  • They may also enhance absorption and storage of lipids: [13]
  • Rodents raised in a sterile environment and lacking in gut flora needed to eat 30% more calories just to remain the same weight as their normal counterparts.

Microbes and the microbiota affect carcinogenesis in three broad ways:[42]
  • altering the balance of tumor cell proliferation and death;
  • regulating immune system function; and
  • influencing metabolism of host-produced factors, foods and pharmaceuticals.


The Gut-Brain Connection: Behaviour, Mood, Stress & Anxiety

Gut microbiota have been shown to be able to activate the vagus nerve, the main line of communication between the gut and the brain. They play a role in regulating how certain mood-regulating chemicals circulate in the blood and brain. They are also interconnected with the immune system, which itself influences mood and behavior. [20]


The blood-brain barrier (BBB) is a highly selective permeable barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system.

  • In 2014, researchers at the Karolinska Institute in Stockholm reported  that germ-free mice (mice raised to have no gut bacteria) had increased BBB permeability as compared to mice with normal gut bacteria. [17]
  • The increased permeability began during gestation and persisted into adulthood. 
  • After the germ-free mice received a fecal transfer from mice with normal gut bacteria, the permeability of their BBB was improved.

Some of the chemicals secreted by gut flora are the same as those used by neurons to communicate and regulate mood; chemicals like dopamine, serotonin and gamma-aminobutyric acid (GABA). [18][44]

  • Lactobacilli rhamnosus, for example, releases immense quantities of GABA, which calms nervous activity. 
  • Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal.
In a study published in 2011, researchers fed a small group of healthy mice a broth infused with Lactobacillus rhamnosus. [18][44]

  • They found that mice fed the broth kept swimming longer and spent less time in a state of immobilized distress, suggesting that signals from gut flora can transmit through the BBB. 

In this 2015 study, researchers found that early life stress can alter gut bacteria in mice and lead to anxiety-like behaviour in adulthood. [21, 22]

  • The study involved subjecting newborn mice to early life stress by separating them from their mothers for several hours a day from day 3 to 21.
  • This resulted in elevated levels of the stress hormone corticosterone, as well as anxious and depression-like behavior.
  • When the experiment was repeated with germ-free mice, the mice did not show any behavioral signs of anxiety or depression. Though, as was the case with the controls, the levels of corticosterone were elevated; that is, the germ-free mice showed chemical, but not behavioral signs of stress.
  • After receiving a transfer of gut flora from normal mice who had been similarly stressed (maternal separation) these germ-free mice did exhibit the abnormal behaviour.
  • However, this gut flora transfer only induced the behavioral change in the germ-free mice who had also previously experienced early life stress as a result of maternal separation.
  • Taken altogether, this suggests that the observed behaviour results from both internal and environmental factors. 

This 2011 study, compared the behavior, brain chemistry and brain development of germ-free mice and mice having normal gut bacteria. [23]

  • Germ-free mice were found to be more active, bolder and less anxious than those with normal gut bacteria.
  • A transfer of gut bacteria from normal mice had no effect on the behavior of the germ-free mice.
  • However, the reverse was the case with the germ-free newborns; suggesting there is a critical period in the development of the brain when the bacteria are influential.
  • These behavioral changes were accompanied by elevated levels of the neurotransmitters dopamine, serotonin and noradrenaline in the region of the brain activated by novel stimuli and associated with the planning and coordination of movement.
  • When the researchers performed a comprehensive gene expression analysis of five different brain regions, they found nearly 40 genes that were affected by the presence of gut bacteria.

This 2015 study looked at whether a prebiotic—a group of carbohydrates that provide nourishment for gut bacteria—affected stress levels among a group of 45 healthy volunteers. [19]

  • Some subjects were fed 5.5 grams of the carbohydrate, galactooligosaccharide (GOS), while others were given a placebo.
  • Subjects who ingested GOS showed lower levels of a key stress hormone, cortisol.
  • In a test involving a series of words flashed quickly on a screen, the GOS group also focused more on positive information and less on negative. 










Anorexia [24]

  • Anorexia nervosa is an eating disorder that affects more than 3 million Americans. It has the highest mortality rate of any psychological disorder.
  • Researchers have found that people with anorexia nervosa have very different microbial communities residing inside their guts compared to healthy individuals, and that this bacterial imbalance is associated with some of the psychological symptoms related to the eating disorder.
  • As the microbial communities in patients with anorexia improved during clinical care and weight gain, the moods of patients also improved.

Antibiotics

  • Antibiotics can also eliminate the good bacteria that keep your digestive system healthy and in balance. Approximately 20% of the population will get antibiotic-associated diarrhea (AAD). [25]
  • Antibiotics can cause AAD by: [39] 
  •  irritating the bowel directly; 
  • changing the levels of gut flora, or 
  • allowing pathogenic bacteria to grow. 
  • Another harmful effect of antibiotics is the increase in numbers of antibiotic-resistant bacteria found after their use, which, when they invade the host, cause illnesses that are difficult to treat with antibiotics. [40]
  • This 2015 study found that a one week course of antibiotics changed participant's gut microbiomes, with the effects sometimes lasting as long as a year. [41]
  • The effects varied depending upon which antibiotic the study participant took (clindamycin, ciprofloxacin, minocycline, and amoxicillin); but generally, while the oral microbiome showed resilience, the same was not the case for flora in the gut.
  • Individuals who took clindamycin and ciprofloxacin saw a decrease in types of bacteria that produce butyrate, a fatty acid that lowers oxidative stress and inflammation in the intestines. 
  • The reduced microbiome diversity for clindamycin-takers lasted up to four months. For some who took ciprofloxacin, it lasted beyond 12 months. 
  • Amoxicillin had no significant effect on either the oral or gut microbiome, and minocycline-takers were back to normal on or before the one month mark.
  • The researchers also found that the number of antibiotic resistant genes in the oral and gut microbiomes of study participants had increased after the course of antibiotics.





Probiotics 

  • Probiotics are live bacteria and yeasts that are good for your health, especially your digestive system. [38]
  • Probiotics are naturally found in your body. 
  • They can also be found in some foods and supplements. 
  • Lactobacillus is found in yogurts and other fermented foods. [38]
  • Bifidobacterium is also found in some dairy products.[38]

  • When you lose good gut flora, probiotic supplements can help replace them.
  • Research suggests it is advantageous to take probiotic supplements along with a course of antibiotics—and for a few weeks after—as they help to keep the gut flora balanced. [25]
  • If you're taking antibiotics, you need a powerful probiotic supplement with at least 5 to 10 billion colony-forming units (CFUs), and they must be live strains. [25]

  • Some conditions they are used to help with include:[38]
  • Irritable bowel syndrome
  • Inflammatory bowel disease
  • Infectious diarrhea
  • Antibiotic-related diarrhea
  • They may also help with skin conditions like eczema, allergies and oral health.


The FDA regulate probiotics like food, not like medications. In general, probiotic foods and supplements are safe, though as with any form of dietary supplement it is best to first consult your physician. [38]
  • It is important to note that none of the supplements or foods that contain probiotics are approved to prevent or treat specific illnesses. [36]
  • Also, that microbe concentrations can also vary widely among products. [36]
  • In 2013 ConsumerLab.com found that out of 19 probiotics tested, 5 contained only 16% to 56% of the listed amounts of organisms. 

The results of this small study (2015) suggests that taking probiotics could make you less stressed and boost your memory. [37]

  • In the study, 22 men were given a capsule containing more than a billion Bifidobacterium longum 1714 bacteria daily for a month, before unknowingly being switched to a placebo for the second month.
  • After the first month, the researchers found that not only did the participants report less stress than both before the trial and during the second month, but they also had lower levels of the stress hormone cortisol in their blood stream.
  • When they were given memory tests that required them to pair objects together, such as a color and a number, the participants also performed better after taking a month of probiotics, as opposed to a month of placebos.
  • Although the study was small, the results did mirror those of previous research on mice which found that probiotics were able to improve their memories and had an antidepressant effect.

In this 2015 study, researchers found that students who ate foods rich in probiotics, such as yogurt, pickles, and sauerkraut, reported feeling less social anxiety and neuroticism. [45]


In this 2013 study, 12 healthy women participants ate a cup of commercially available probiotic yogurt twice a day for four weeks, while 13 healthy woman participants didn’t. [19][25]

  • The probiotic yogurt contained the following live species of bacteria: bifidobacterium, streptococcus, lactococcus, and lactobacillus
  • Before and after the study, subjects were given brain scans to gauge their response to a series of images of facial expressions—happiness, sadness, anger, and so on.
  • The results showed significant differences between the two groups; the yogurt eaters reacting more calmly to the images than the control group. 

Autism [19]
Although autism spectrum disorder (ASD) is defined by core behavioral impairments, it is estimated that three-quarters of people with autism also have some gastrointestinal abnormality, like digestive issues, food allergies, or gluten sensitivity.  
In this 2013 study, researchers fed human commensal Bacteroides fragilis to mice with symptoms similar to autism. 
  • The treatment altered the makeup of the animals’ microbiome, corrected gut permeability, and improved ASD-related behaviors: They became less anxious, communicated more with other mice, and showed less repetitive behavior. 


Gastric Bypass, Diet & Obesity

This 2015 study researchers transplanted bacteria from obese women and from women who had the surgeries (Roux-en-Y gastric bypass or gastric banding) into germ-free mice. [27]

  • Mice with gut bacteria from the surgery groups gained less body fat than did rodents with microbes transplanted from obese women.
  • Gastric bypass in particular switched the metabolism of microbes so that they burned fewer carbohydrates and more fat. 

In this study (2015), researchers found that diets high in fat radically changed the native populations of bacteria residing inside the guts of rats, which in turn may interfere with the brain’s ability to stop the body from overeating. [28]
The rats had one of two meal plans:

  • A regular diet with a daily fat content of about 6%
  • A diet with a daily fat content of about 35%
In the rats consuming the high fat diet, some bacteria began to overpopulate, and some sensitive bacteria began to die.

Researchers also found that there was noticeable changes along certain neural pathways:

"The brain is changed by eating unbalanced foods. It induces inflammation in the brain regions responsible for feeding behavior. Those reorganized circuits and inflammation may alter satiety signaling." [Krzysztof Czaja, Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA]


This 2015 study investigated what changes in diet do to one particular gut microbe species: Akkermansia muciniphila—a strain that’s been associated with leanness and better glucose tolerance in mice. [29]

  • 49 overweight and obese adults followed a six-week calorie reduced diet while increasing their fiber intake. The diet was followed by six weeks of eating normally.
  • Participants who had more Akkermansia in their gut from the very start had better clinical measures after they completed the diet, compared to the people with less of the bacterium.
  • Both groups of people lost the same amount of weight, but the high-Akkermansia group had a stronger decrease in visceral fat, improved cholesterol and glycemia, than the others.
  • People who started out with lower stores of Akkermansia had more after they followed the fiber-rich calorie-restricted diet. 

A few words on fiber: 

  • Gut microbes feed on fiber and produce short-chain fatty acids, which get absorbed into the bloodstream and regulate the immune system. [29]
  • When mice eat food depleted of dietary fiber, their gut microbes,  
“ ... turn and start eating the mucus lining of the intestine because that’s also a carbohydrate source and it’s kind of a fallback food for them. … In mice on a low-fiber diet, the mucus lining thins to about half of its normal width. 
... All of the vegetables we’re encouraged to eat by our mothers and by the government guidelines, these are all filled with fiber, and filled with a diversity of fiber, and probably the best route for encouraging a diverse microbiota.”  
[Justin L. Sonnenburg, PhD, associate professor in the department of microbiology and immunology at Stanford University School of Medicine and author of The Good Gut.]

  •  Fiber-fortified processed foods haven’t be found to have the same effects as fiber that occur naturally in whole foods like vegetables. [29]




Seven Foods to Supercharge Your Gut Bacteria / Physicians Committee for Responsible Medicine



  • In genetically engineered obese mice, scientists found that a class of gut microbes called Firmicutes was consistently over-represented. [30] 
  • And that the Firmicutes were too efficient at extracting energy from food, breaking down fiber and even increasing the absorption of dietary fat
  • In this way, gut microbes could cause retention of body weight without the animal eating an extra morsel of food. 
  • Investigators were also able to transfer obesity to germ-free mice via *fecal transplantation from obese mouse donors.

*Fecal transplantation (or bacteriotherapy) is the transfer of stool from a healthy donor into the gastrointestinal tract for the purpose of treating recurrent C. difficile colitis. [www.hopkinsmedicine.org/gastroenterology.../fecal_transplantation.html] ... More on this later.



In numerous studiesincluding twin studies [3][26], obesity was associated with a significantly reduced biodiversity of the gut ecosystem[30]
"In addition to breaking down fiber faster and absorbing more fat, the unbalanced mix of gut microbes no longer represents a well-diversified ecosystem that regulates immunity. Rather, it fosters inflammation and the loosening of the tight junctions that hold together the cells in the intestinal liningThis causes bacterial toxins to seep out into the body, where they act on our genes, promoting an unhealthy inflammatory response.
This results in a number of biochemical events that foster fat accumulation, hyperglycemia, insulin resistance, and more." 


Researchers have found that juvenile rats who voluntarily exercised every day developed a more beneficial microbial structure, including the expansion of probiotic bacterial species in their gut compared to both their sedentary counterparts and adult rats, even when the adult rats exercised as well. [31]


Researchers (2015) have found that cold exposure dramatically alters the composition of intestinal bacteria in mice and that this microbial shift is sufficient to burn fat, improve glucose metabolism, and reduce body weight. [32]

  • However, after three weeks of cold exposure body weight began to stabilize. This stabilization may have occurred due to an increased absorption of nutrients in the intestine, counteracting additional weight loss that would otherwise result from higher overall energy expenditure. 


Pregnancy, Birth & Breastfeeding


The microbiome is likely to have its greatest impact early in life. [9-11]

  • During vaginal birth and rapidly thereafter, bacteria from the mother and the surrounding environment colonize the infant’s gut. [9-10]

Infants born by caesarean section may also be exposed to their mother’s microbiota, but the initial exposure is most likely to be from the surrounding environment. [9-11] 


Using an established mouse model of early maternal stress, researchers have found (2015) that maternal stress can alter the gut and brain of offspring via the vaginal microbiome. [33]
"As the neonate's gut is initially populated by the maternal vaginal microbiome, changes produced by maternal stress can alter this initial microbe population as well as determine many aspects of the [baby's] immune system that are also established during this early period." 
[Tracy Bale, PhD, of the University of Pennsylvania] 

In this study (2015), the stress and anxiety levels of pregnant women were measured by means of questionnaires and testing the levels of the hormone cortisol in saliva. [34]

  • In addition, faeces samples from 56 babies were tested from 7 days until 4 months after birth.

  • Mothers who reported high stress levels and presented high cortisol readings had babies with more Proteobacteria and fewer lactic acid bacteria and Actinobacteria in their microbiota. 
  • This represents a poor mix of microbiota, which was also reflected in the relationship between the presence of these microbiota and a higher incidence of intestinal problems and allergic reactions among the babies in this research group. 


In this 2015 asthma study, in which 319 babies were followed from age three months to 1 year, researchers found that the wheezy babies were more likely to be missing four types of bacteria: [46]
Lachnopsira, Veillonella, Faecalibacterium and Rothia. 
  • When a germ-free pregnant mouse was inoculated with microbes from the feces of a three month old human infant with low levels of the four bacteria, the mouse pups developed asthma.
  • But if the mouse mother’s inoculum was supplemented with the four bacteria, her pups were protected.
  • The research also suggested that the opportunity for these bacteria to modify the immune system from an allergic state to a non-allergic one, seems to lie within the first 100 days of life. 
  • While the microbial communities of the three month old babies showed differences, by the time they were a year old, those differences had almost vanished.


This 2014 study shows that breastfeeding promotes the growth of beneficial lactic acid bacteria in the baby's gut flora, which are beneficial to the development of the child's immune system. [35]
A number of studies have shown that breastfed babies grow slightly slower and are slightly slimmer than children who are fed with infant formula. Children who are breastfed also have a slightly lower incidence of obesity, allergies, diabetes and inflammatory bowel disease later in life.
The study shows that there are significant changes in the intestinal bacterial composition from nine to 18 months following cessation of breastfeeding and other types of food being introduced. However, a child's gut microbiota continues to evolve right up to the age of three, as it becomes increasingly complex and also more stable. [35]


Fecal Transfer 


Bacteria found in a sample of human feces. [46]
CREDIT: EYE OF SCIENCE/GETTY IMAGE

From: [Science says a poo transplant taken through the nose works better than antibiotics / CHRIS PASH / Business Insider /October 25, 2015 via sciencealert.com]


  • Fecal transplants are currently being used to treat severe bacterial infections. As the name implies, feces from a healthy donor is added to the patient’s bowel, either by tube through the nose or via the rectum.
  • The method, which colonizes the gut with healthy bacteria, has an 85% success rate against life-threatening infections such as Clostridium compared to only 20% for standard antibiotic treatment.
  • More than 500 centers in the US now offer fecal transplantation, with most using frozen donations from the not-for-profit stool bank organization, OpenBiome, in Boston. The UK regulator (MRHA) has temporarily classed fecal transplants as a medicinal product.




Updates/Related:

Low-Fiber Diets Cause Waves of Extinction in the Gut / theatlantic.com/ January 13, 2016

Does our Microbiome Control Us or Do We Control It? / scientificamerican.com/January 13, 2016

Human trials will test freeze-dried poop pills as a weight-loss treatment / sciencealert.com/January 12, 2016





***FIN***








REFERENCES

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[7]  Segal, Leopoldo; Blaser, Martin (2014). "A Brave New World: The Lung Microbiota in an Era of Change". Annals of the American Thoracic Society 11: S21–S27.doi:10.1513/AnnalsATS.201306-189MG
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[9] https://en.wikipedia.org/wiki/Gut_flora
[10] Bettelheim, K. A.; Breadon, Alwena; Faiers, Mary C.; O'Farrell, Sheila M.; Shooter, R. A. (2009). "The origin of O serotypes of Escherichia coli in babies after normal delivery".Journal of Hygiene 72 (1): 67–70. doi:10.1017/S0022172400023226PMC 2130250.PMID 4593741.
[11] Schwiertz, Andreas; Gruhl, Bärbel; Löbnitz, Manuela; Michel, Peter; Radke, Michael; Blaut, Michael (2003). "Development of the Intestinal Bacterial Composition in Hospitalized Preterm Infants in Comparison with Breast-Fed, Full-Term Infants". Pediatric Research 54(3): 393–9. doi:10.1203/01.PDR.0000078274.74607.7APMID 12788986.
[12] Guarner, F; Malagelada, J (2003). "Gut flora in health and disease". The Lancet 361 (9356): 512–9. doi:10.1016/S0140-6736(03)12489-0PMID 12583961.
[13] Sears, Cynthia L. (2005). "A dynamic partnership: Celebrating our gut flora". Anaerobe 11 (5): 247–51. doi:10.1016/j.anaerobe.2005.05.001.PMID 16701579.
[14] Keeley J. 2004. Good bacteria trigger proteins to protect the gut. Howard Hughes Medical Institute. EurekAlert. 
[15] Kiger, Patrick J..  "How long does it take gut flora to recover from antibiotics?"  30 April 2015.  HowStuffWorks.com. <http://health.howstuffworks.com/medicine/medication/long-does-it-take-gut-flora-to-recover-from-antibiotics.htm>  04 January 2016.
[16] Gibson, Glenn R. (2004). "Fibre and effects on probiotics (the prebiotic concept)". Clinical Nutrition Supplements 1 (2): 25–31. doi:10.1016/j.clnu.2004.09.005.
[17] How Gut Bacteria Protect The Brain / http://www.drperlmutter.com/gut-bacteria-protects-brain/
Journal Source: 
The gut microbiota influences blood-brain barrier permeability in mice / Viorica Braniste et al. / Sci Transl Med 6. 263ra158 (2014); DOI: 10. 1126/ scitranslmed.3009759

[18] University College Cork. "Mind-altering microbes: Probiotic bacteria may lessen anxiety and depression." ScienceDaily. ScienceDaily, 30 August 2011. <www.sciencedaily.com/releases/2011/08/110829164601.htm>.

Journal Reference:

Javier A. Bravo, Paul Forsythe, Marianne V. Chew, Emily Escaravage, Hélène M. Savignac, Timothy G. Dinan, John Bienenstock, John F. Cryan. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1102999108

[19] When Gut Bacteria Changes Brain Function / theatlantic.com /June 24, 2015
Journal Reference:

Hsiao, Elaine Y. et al. “The Microbiota Modulates Gut Physiology and Behavioral Abnormalities Associated with Autism.” Cell 155.7 (2013): 1451–1463. PMC. Web. 4 Jan. 2016.

[20] How the bacteria in your stomach are connected to your mood / By Kevin Loria / World Econoic Forum / July 23, 2015
[21] McMaster University. "Link between intestinal bacteria, depression found." ScienceDaily. ScienceDaily, 28 July 2015. http://www.sciencedaily.com/releases/2015/07/150728110734.htm

Journal Reference:

G. De Palma, P. Blennerhassett, J. Lu, Y. Deng, A. J. Park, W. Green, E. Denou, M. A. Silva, A. Santacruz, Y. Sanz, M. G. Surette, E. F. Verdu, S. M. Collins, P. Bercik. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nature Communications, 2015; 6: 7735 DOI: 10.1038/ncomms8735

[22] Could gut bacteria help make you more anxious? / By Bianca Nogrady / abc.net.au / July 29. 2015
[23] The Neuroscience of the Gut / http://www.scientificamerican.com/article/the-neuroscience-of-gut/
[24] University of North Carolina Health Care. "Gut bacteria population, diversity linked to anorexia nervosa: Studying the 'gut-brain axis,' researchers find evidence of an association." ScienceDaily. ScienceDaily, 5 October 2015. <http://www.sciencedaily.com/releases/2015/10/151005121310.htm>.
[25] Cooper, Alison.  "Should you take antibiotics and probiotics at the same time?"  10 April 2015.  HowStuffWorks.com. <http://health.howstuffworks.com/medicine/medication/antibiotics-probiotics-same-time.htm>  04 January 2016.
[26] Turnbaugh, P. J.; Hamady, M.; Yatsunenko, T.; Cantarel, B. L.; Duncan, A.; Ley, R. E.; Sogin, M. L.; Jones, W. J.; Roe, B. A.; Affourtit, J. P.; Egholm, M.; Henrissat, B.; Heath, A. C.; Knight, R.; Gordon, J. I. (2008). "A core gut microbiome in obese and lean twins". Nature 457 (7228): 480–484. doi:10.1038/nature07540PMC 2677729.PMID 19043404.
[27] Gastric bypass surgery changes gut microbes / BY TINA HESMAN SAEY  / sciencenews.org / August 5, 2015

Study Reference:

Czaja K, Vaughn AC, Dilorenzo PM, et al. Diet-induced obesity is associated with a change in the intestinal microbiota, activation of microglia, and reorganization of the nucleus of the solitary tract. SSIB 2015.

Journal Reference:
Dao MC, Everard A, AronWisnewsky J, et al. Gut Published Online First: [please include Day Month Year] doi:10.1136/gutjnl- 2014-308778
[31] University of Colorado at Boulder. "Early-life exercise alters gut microbes, promotes healthy brain and metabolism." ScienceDaily. ScienceDaily, 29 December 2015. <www.sciencedaily.com/releases/2015/12/151229204252.htm>.

Journal Reference:

Agnieszka Mika, Monika Fleshner. Early life exercise may promote lasting brain and metabolic health through gut bacterial metabolites. Immunology and Cell Biology, 2015; DOI:10.1038/icb.2015.113

[32] Cell Press. "Gut microbes trigger fat loss in response to cold temperatures." ScienceDaily. ScienceDaily, 3 December 2015. <www.sciencedaily.com/releases/2015/12/151203135832.htm>.

Journal Reference:

Claire Chevalier, Ozren Stojanović, Didier J. Colin, Nicolas Suarez-Zamorano, Valentina Tarallo, Christelle Veyrat-Durebex, Dorothée Rigo, Salvatore Fabbiano, Ana Stevanović, Stefanie Hagemann, Xavier Montet, Yann Seimbille, Nicola Zamboni, Siegfried Hapfelmeier, Mirko Trajkovski.Gut Microbiota Orchestrates Energy Homeostasis during Cold. Cell, 2015; 163 (6): 1360 DOI: 10.1016/j.cell.2015.11.004

[33] Endocrine Society. "Maternal stress alters offspring gut, brain through vaginal microbiome." ScienceDaily. ScienceDaily, 16 June 2015. <www.sciencedaily.com/releases/2015/06/150616131532.htm>.

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Eldin Jašarević, Christopher L. Howerton, Christopher D. Howard, and Tracy L. Bale. Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain. Endocrinology, June 2015 DOI:10.1210/en.2015-1177

[34] Radboud University. "Stress during pregnancy related to infant gut microbiota." ScienceDaily. ScienceDaily, 26 January 2015. <www.sciencedaily.com/releases/2015/01/150126095425.htm>.

Journal Reference:

Maartje A.C. Zijlmans, Katri Korpela, J. Marianne Riksen-Walraven, Willem M. de Vos, Carolina de Weerth. Maternal Prenatal Stress is Associated with the Infant Intestinal Microbiota.Psychoneuroendocrinology, 2015; DOI: 10.1016/j.psyneuen.2015.01.006

[35] Technical University of Denmark (DTU). "Breastfeeding promotes growth of beneficial bacteria in gut." ScienceDaily. ScienceDaily, 7 May 2014. <www.sciencedaily.com/releases/2014/05/140507095910.htm>.

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A. Bergstrom, T. H. Skov, M. I. Bahl, H. M. Roager, L. B. Christensen, K. T. Ejlerskov, C. Molgaard, K. F. Michaelsen, T. R. Licht. Establishment of Intestinal Microbiota during Early Life: a Longitudinal, Explorative Study of a Large Cohort of Danish Infants. Applied and Environmental Microbiology, 2014; 80 (9): 2889 DOI:10.1128/AEM.00342-14

[36] Don't Be Fooled: 5 Probiotics Myths/ By Cari Nierenberg, Contributing Writer / livescience.com/ July 03, 2014
[39] Beaugerie, Laurent; Petit, Jean-Claude (2004). "Antibiotic-associated diarrhoea". Best Practice & Research Clinical Gastroenterology 18 (2): 337–52.doi:10.1016/j.bpg.2003.10.002PMID 15123074.
[40] Carman, Robert J.; Simon, Mary Alice; Fernández, Haydée; Miller, Margaret A.; Bartholomew, Mary J. (2004). "Ciprofloxacin at low levels disrupts colonization resistance of human fecal microflora growing in chemostats". Regulatory Toxicology and Pharmacology 40 (3): 319–26. doi:10.1016/j.yrtph.2004.08.005PMID 15546686.
[42] Garrett, Wendy S. (3 April 2015). "Cancer and the microbiota". Science Magazine. doi:10.1126/science.aaa4972
[43] Seven Foods to Supercharge Your Gut Bacteria / Physicians Committee for Responsible Medicine Also
[44] Can the Bacteria in YourGut Explain Your Mood? / By PETER ANDREY SMITH / nytimes.com / June 23, 2015
smithsonian.com / June 22, 2015

Journal Source:

Fermented foods, neuroticism, and social anxiety: An interaction model. Hilimire MR1, DeVylder JE2, Forestell CA3. Psychiatry Res. 2015 Aug 15;228(2):203-8. doi: 10.1016/j.psychres.2015.04.023. Epub 2015 Apr 28.


[46] The four bugs that protect us from asthma/ By Elizabeth Finkel / cosmosmagazine.com / November 30, 2015

Journal Source:

By Marie-Claire Arrieta, Leah T. Stiemsma, Pedro A. Dimitriu, Lisa Thorson, Shannon Russell, Sophie Yurist-Doutsch, Boris Kuzeljevic, Matthew J. Gold, Heidi M. Britton, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker,Kelly M. Mcnagny, Malcolm R. Sears, Tobias Kollmann, The Child Study Investigators, William W. Mohn, Stuart E. Turvey, B. Brett Finlay; SCIENCE TRANSLATIONAL MEDICINE 30 SEP 2015 : 307RA152




IMAGE CREDITS:

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"Blausen 0432 GastroIntestinalSystem" by BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work. Licensed under CC BY 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Blausen_0432_GastroIntestinalSystem.png#/media/File:Blausen_0432_GastroIntestinalSystem.png

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Seven Foods to Supercharge Your Gut Bacteria / Physicians Committee for Responsible Medicine
Consumer Reports Health / Five Questions to Ask Your Doctor About Antibiotics

Bacteria found in a sample of human fecesCREDIT: EYE OF SCIENCE/GETTY IMAGE