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Winterize Your Immune System

chilly-womanThe relationship between vitamin D status and the strength of the immune system is a hot topic. Actually a steroid hormone more than a vitamin, vitamin D is made by the skin after exposure to the ultraviolet radiation of the sun. Because the sun’s angle of incidence outside the tropics is considerably lower in winter, the skin’s response is too weak to manufacture sufficient stores of this vital nutrient.

In the early 1980’s, British physician R. Edgar Hope-Simpson proposed a relationship between solar radiation and the seasonality of influenza.  Without sufficient sunlight, the skin does not produce vitamin D, deficiency of which is common in winter.  This steroid hormone has considerable influence on immunity, where it prevents excessive expression of inflammation and is able to, “…stimulate the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection.”   (Cannell. 2006)   This study, performed at California’s Atascadero State Hospital, states that deficiency of vitamin D predisposes children to respiratory infections.  UV radiation, either natural or artificial, increases vitamin D levels and thereby reduces the incidence of pulmonary infections.

Vitamin D deficiency has been associated with many of the diseases of modern society, but traditional medicine has been reluctant to address this concern, or even to recognize it.  This vitamin is the only known precursor to a potent steroid hormone that is able to regulate expression in a number of tissues.  It does not exist in appreciable amounts in the diet, not even in fortified foods like dairy.  People used to make enormous amounts of vitamin D until they were warned to stay out of the sun.  If not exposed to the sun, we need to get it from supplements.  The flu epidemic of 1918 took a great toll.  Autopsies on some of the fifty million people who died revealed destruction of the respiratory tract.  This is the inflammation that vitamin D has been found to prevent.

Randomized, double-blind, placebo-controlled studies done in Japan in 2010 found that vitamin D3 supplementation not only reduced incidence of influenza type A, but also reduced asthma attacks as a secondary outcome. (Urashima. 2010).  The elderly tend to have suboptimal levels of vitamin D, which is associated with an increased risk of falls as well as seasonal virus attacks.  Vitamin D supplementation in this group is a realistic intervention that can pay large dividends.  2000 IU a day has been suggested as a minimal dose also to help prevent osteoporosis, increased risk of certain cancers, aberrant glucose and lipid metabolism and to improve quality of life.  (Lawless. 2011)  (Cherniak.  2008). Solar activities of the sun have a cycle of about eleven years, and an interesting phenomenon is that flu epidemics seems to follow the pattern.  (Hayes.  2010).

Vitamin D is not the sole player in the winterizing game.  Viruses need to get into your cells to make copies of themselves, using your cellular materials.   Replication of the flu virus is interrupted by a standardized elderberry extract called Sambucol, the use of which brought improvement to more than 90% of the persons in a study group within two days.  Since there is no satisfactory medication to cure the flu, this natural substance is nearly miraculous because it’s also inexpensive, has no side effects, and works on both A and B strains of influenza.  (Zakay-Rones.  1995)  (Zakay-Rones.  2004). The anti-viral properties of elderberry are attributed to its flavonoids content, some of which are peculiar to that plant alone. (Roschek. 2009).

A considerable part of the immune system resides in the gut, where intestinal microflora work to maintain the status quo.  Keeping those bacteria happy and healthy makes sense, so probiotics have been examined as a support system.  In a controlled study in Wisconsin, scientists found that six months of supplementation with a probiotic resulted in reduced fever, runny nose, and cough incidence in youngsters aged 3 to 5 years.  Duration of prescription medications and missed school days also were reduced.  (Leyer. 2009)  Day care centers across the Atlantic also fared well in the reduction of childhood infections with probiotic use. In Finland, researchers saw a substantial reduction in respiratory infections and their severity among children under 6 years old, accompanied by a reduction in the need for antibiotic treatment in those who received probiotic dairy products.  (Hatakka.  2001)

Investigations of echinacea as treatment for flu were not as positive as those for prevention.  It was discovered that early intervention, at the fist symptoms, brought the best results using an echinacea compound tea, namely one called Echinacea Plus.  (Lindenmuth.  2000).  Because there are too many variables, including the part or parts of the plant used, the brewing times and techniques, the variety of the plant used, its cultivation conditions, and other factors, test results are likely to differ.  Even in trials with sound methodology, results may conflict.  (Melchart.  2000)  (Linde. 2006) Using echinacea as prevention or as treatment, then, may be an uncertain proposition.

There is more to consider.  Garlic and onions have putative anti-bacterial and anti-viral properties. (Goncagul. 2010). (Harris. 2001)  Exercise, regardless of intensity or duration, and sound sleep of uninterrupted duration help the lymphatic system to clear impurities and to boost immunity.  One or all of these suggestions might be your ounce of prevention.  Oh, yeah, one last thing.  The higher the humidity in your house in the winter, the less likely viruses are to be transmitted.  (Lowen,. 2007)  (Yang. 2011)

References

MAIN ABSTRACT
Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40.

SUPPORTING ABSTRACTS
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H.
Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
Am J Clin Nutr. 2010 May;91(5):1255-60. Epub 2010 Mar 10.

Lawless S, White P, Murdoch P, Leitch S.
(Preventing) two birds with one stone: improving vitamin D levels in the elderly.
J Prim Health Care. 2011 Jun 1;3(2):150-2.

Cherniack EP, Levis S, Troen BR.
Hypovitaminosis D: a widespread epidemic.
Geriatrics. 2008 Apr;63(4):24-30.

Hayes DP.
Influenza pandemics, solar activity cycles, and vitamin D.
Med Hypotheses. 2010 May;74(5):831-4. Epub 2009 Dec 28.

Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M.
Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama.
J Altern Complement Med. 1995 Winter;1(4):361-9.

Zakay-Rones Z, Thom E, Wollan T, Wadstein J.
Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.
J Int Med Res. 2004 Mar-Apr;32(2):132-40.

Roschek B Jr, Fink RC, McMichael MD, Li D, Alberte RS.
Elderberry flavonoids bind to and prevent H1N1 infection in vitro.
Phytochemistry. 2009 Jul;70(10):1255-61.

Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC
Probiotic effects on cold and influenza-like symptom incidence and duration in children.
Pediatrics. 2009 Aug;124(2):e172-9.

Hatakka K, Savilahti E, Pönkä A, Meurman JH, Poussa T, Näse L, Saxelin M, Korpela R.
Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial.
BMJ. 2001 Jun 2;322(7298):1327

Brinkeborn RM, Shah DV, Degenring FH.
Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial.
Phytomedicine. 1999 Mar;6(1):1-6.

Lindenmuth GF, Lindenmuth EB
The efficacy of echinacea compound herbal tea preparation on the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebo-controlled study.
J Altern Complement Med. 2000 Aug;6(4):327-34.

Melchart D, Linde K, Fischer P, Kaesmayr J.
Echinacea for preventing and treating the common cold.
Cochrane Database Syst Rev. 2000;(2):CD000530.

Linde K, Barrett B, Wölkart K, Bauer R, Melchart D.
Echinacea for preventing and treating the common cold.
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD000530.

Goncagul G, Ayaz E.
Antimicrobial effect of garlic (Allium sativum).
Recent Pat Antiinfect Drug Discov. 2010 Jan;5(1):91-3.

Harris JC, Cottrell SL, Plummer S, Lloyd D.
Antimicrobial properties of Allium sativum (garlic).
Appl Microbiol Biotechnol. 2001 Oct;57(3):282-6.

Lowen AC, Mubareka S, Steel J, Palese P.
Influenza virus transmission is dependent on relative humidity and temperature.
PLoS Pathog. 2007 Oct 19;3(10):1470-6.

Wan Yang, Linsey C. Marr
Dynamics of Airborne Influenza A Viruses Indoors and Dependence on Humidity
PLoS ONE: Research Article, published 24 Jun 2011 10.1371/journal.pone.0021481

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Antibiotic Alternatives

garlic-goldensealLivestock and poultry live in such proximity to each other that they share more than food. They stand in it, they wallow in it, and they breathe it.  How does the farmer in the dell protect his animals from catching each other’s sicknesses and diseases?  From cattle to chickens, and probably even to farmed fish, antibiotics have been necessary evils, having resulted in tremendous increases in animal production and protection of human health.  (Hume. 2011)  It’s been a rare case when these drugs weren’t used.  Some factory farms that swore they were antibiotic free were later found to be in violation of the truth.  Primary care physicians prescribe antibiotics to satisfy their patients’ false beliefs that this class of drug will cure their common cold and remove symptoms of influenza.  (Smucny. 2000)  What’s wrong with this?  Antibiotic resistance is the concern, an issue that develops almost too quickly for science to keep ahead of the pathogens. (Hall. 2004)

Enter the alternatives—the natural antibiotics.

For a reason not yet identified, bacteria have a tough time becoming resistant to natural substances.  Maybe we shouldn’t look a gift horse in the mouth.  Because they are natural, these alternative antibiotics / antivirals cannot be patented.  They are dose-dependent, as well, meaning that you might need more of a substance than your twin brother or sister.  The bacteria we face today are the same ones we faced in past decades, but they don’t die at the hands of the miracle drugs that worked sixty years ago.  These potential killers have been found to fall at the hands of some pretty innocuous characters.  Here are a few.

Goldenseal, the most active compound of which is called berberine, is a supplement that reduces the ability of some streptococcus bacteria to adhere to epithelial cells, the covering of organs that compares to skin.  Berberine is bactericidal and bacteriostatic, killing and preventing bacterial multiplication.  (Sun. 1988)  (Amin. 1969)  In tests at California’s Veterans Affairs Medical Center at San Diego, staff discovered that goldenseal was able to increase antigen-specific immunoglobin (Ig) production, namely IgM, the immunoglobin that responds first to intrusion by pathogens in the bloodstream.  In combination with echinacea (angustifolia), an augmentation of IgG response was noted, thus making invaders subject to destruction by macrophages.  (Rehman. 1999)

Essential oils and extracts from plants have been recognized as being antimicrobial for many years.  They haven’t been studied extensively because there is little profit in substances that can’t be patented.  Pharmaceutical companies have major dollars available for research, but not for anything that grows in your yard.  In 1999, the University of Western Australia pulled out all the stops and investigated more than fifty plant oils and extracts for their efficacy as antimicrobial agents.  No less than ten common bacteria strains fell prey to oils lemongrass, oregano, and bay, including E. coli, Candida albicans, Staphylococcus aureus, and two pneumonia bacteria.  The remaining oils and extracts showed variable activity, but the notion of using plant oils as pharmaceutical agents was supported.  (Hammer. 1999)  A year later, in the UK, Scots found that “volatile oils exhibited considerable inhibitory effects against all the organisms under test…” (Dorman. 2000)

A perpetual favorite, garlic is one of the better-known and more frequently enlisted of the antiviral compounds.  One of the neatest stories about this plant is that the crooks who wandered Europe during the Black Death rampage of the 14th century survived the plague only because garlic was a mainstay of their diets.  At the end of the last century it was ascertained effective against E.coli in work conducted at Hirosaki University in Japan.  (Sasaki. 1999)   Fresh garlic was used in those tests and in earlier American studies at Brigham Young University, where garlic thiosulfates demonstrated virucidal properties against every strain of virus tested. (Weber. 1992)  Even MRSA is controllable with garlic given at twelve-hour intervals.  (Tsao.  2007)  This seems too simple.

Staphylococcus aureus, the villain of MRSA fame, succumbed to just the vapors exuded by a combined grapefruit seed extract and geranium oil extract in experiments done with burn dressings at a British hospital in 2004. (Edwards-Jones. 2004)  Studies on echinacea are fraught with controversy because of inconsistencies in methodology.  The plant responds to variations in cultivation factors that include weather, soil type, irrigation, fertilizers, and more.  The species and the parts of the plant used, and processing measures, make a difference in outcomes.  Generally, echinacea is better at prevention than cure, although it may relieve the common cold a few days sooner. (Schulten. 2001)  Used for respiratory infections, it may have no benefit at all. (Barrett. 1999)  Maybe a positive expectation makes a difference.  Whatever message you take home from this, don’t ask your doctor for an antibiotic to treat your runny nose, sore throat and fever.

References

MAIN ABSTRACTS
Hume ME.
Historic perspective: Prebiotics, probiotics, and other alternatives to antibiotics.
Poult Sci. 2011 Nov;90(11):2663-9.

Smucny J, Fahey T, Becker L, Glazier R, McIsaac W.
Antibiotics for acute bronchitis.
Cochrane Database Syst Rev. 2000;(4):CD000245.

Barry G. Hall
Predicting the evolution of antibiotic resistance genes
Nature Reviews Microbiology 2, 430-435 (May 2004)

SUPPORTING ABSTRACTS
Sun D, Courtney HS, Beachey EH.
Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane.
Antimicrob Agents Chemother. 1988 Sep;32(9):1370-4.

Amin AH, Subbaiah TV, Abbasi KM.
Berberine sulfate: antimicrobial activity, bioassay, and mode of action.
Can J Microbiol. 1969 Sep;15(9):1067-76.

Rehman J, Dillow JM, Carter SM, Chou J, Le B, Maisel AS.
Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis
Immunol Lett. 1999 Jun 1;68(2-3):391-5.

Hammer KA, Carson CF, Riley TV.
Antimicrobial activity of essential oils and other plant extracts.
J Appl Microbiol. 1999 Jun;86(6):985-90.

Dorman HJ, Deans SG.
Antimicrobial agents from plants: antibacterial activity of plant volatile oils.
J Appl Microbiol. 2000 Feb;88(2):308-16.

Sasaki J, Kita T, Ishita K, Uchisawa H, Matsue H.
Antibacterial activity of garlic powder against Escherichia coli O-157.
J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):785-90.

Tsao SM, Liu WH, Yin MC.
Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice.
J Med Microbiol. 2007 Jun;56(Pt 6):803-8.

Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG.
In vitro virucidal effects of Allium sativum (garlic) extract and compounds
Planta Med. 1992 Oct;58(5):417-23.

Edwards-Jones V, Buck R, Shawcross SG, Dawson MM, Dunn K.
The effect of essential oils on methicillin-resistant Staphylococcus aureus using a dressing model.
Burns. 2004 Dec;30(8):772-7.

Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D’Alessio D.
Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial.
Ann Intern Med. 2002 Dec 17;137(12):939-46.

Schulten B, Bulitta M, Ballering-Brühl B, Köster U, Schäfer M.
Efficacy of Echinacea purpurea in patients with a common cold. A placebo-controlled, randomised, double-blind clinical trial.
Arzneimittelforschung. 2001;51(7):563-8.

Barrett B, Vohmann M, Calabrese C.
Echinacea for upper respiratory infection.
J Fam Pract. 1999 Aug;48(8):628-35.

Blaser M.
Antibiotic overuse: Stop the killing of beneficial bacteria.
Nature. 2011 Aug 24;476(7361):393-4. doi: 10.1038/476393a.

Arnold SR, Straus SE.
Interventions to improve antibiotic prescribing practices in ambulatory care.
Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003539.

Zenner D, Shetty N.
European Antibiotic Awareness Day 2011: antibiotics–a powerful tool and a dwindling resource.
Fam Pract. 2011 Oct;28(5):471-3.

Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS.
Fluoroquinolone prescribing in the United States: 1995 to 2002.
Am J Med. 2005 Mar;118(3):259-68.

Smucny J, Fahey T, Becker L, Glazier R, McIsaac W.
Antibiotics for acute bronchitis.
Cochrane Database Syst Rev. 2000;(4):CD000245.

Hueston WJ.
Antibiotics: neither cost effective nor ‘cough’ effective
J Fam Pract. 1997 Mar;44(3):261-5.

Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP.
Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.
JAMA. 2003 Feb 19;289(7):885-8.

Harrison JW, Svec TA.
The beginning of the end of the antibiotic era? Part II. Proposed solutions to antibiotic abuse.
Quintessence Int. 1998 Apr;29(4):223-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.

References

Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5. doi: 10.1016/j.appet.2011.01.016. Epub 2011 Jan 19.

Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB.
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.
Cell Host Microbe. 2012 Nov 15;12(5):611-22.

Beaugerie L, Petit JC.
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea.
Best Pract Res Clin Gastroenterol. 2004 Apr;18(2):337-52.

Bischoff SC.
‘Gut health’: a new objective in medicine?
BMC Med. 2011 Mar 14;9:24.

Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS, Frokiaer H, Heinrich J, Garn H, et al
Early nutrition and immunity – progress and perspectives.
Br J Nutr. 2006 Oct;96(4):774-90.

Roberto Berni Canani, Margherita Di Costanzo, and Ludovica Leone
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Clin Epigenetics. 2012; 4(1): 4.

Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, et al
PASSCLAIM–gut health and immunity.
Eur J Nutr. 2004 Jun;43 Suppl 2:II118-II173.

de Vrese M, Schrezenmeir J.
Probiotics, prebiotics, and synbiotics.
Adv Biochem Eng Biotechnol. 2008;111:1-66. doi: 10.1007/10_2008_097.

Fanaro S, Chierici R, Guerrini P, Vigi V.
Intestinal microflora in early infancy: composition and development
Acta Paediatr Suppl. 441: 48-55. 2003

Flint HJ, Scott KP, Louis P, Duncan SH.
The role of the gut microbiota in nutrition and health.
Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):577-89.

Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP, Sanderson IR.
Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.
Mol Med. 1999 Sep;5(9):631-40.

Gamet L, Daviaud D, Denis-Pouxviel C, Remesy C, Murat JC.
Effects of short-chain fatty acids on growth and differentiation of the human colon-cancer cell line HT29.
Int J Cancer. 1992 Sep 9;52(2):286-9.

Garcovich M, Zocco MA, Roccarina D, Ponziani FR, Gasbarrini A.
Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota.
World J Gastroenterol. 2012 Dec 14;18(46):6693-700. doi: 10.3748/wjg.v18.i46.6693.

Guarner F, Malagelada JR.
Gut flora in health and disease.
Lancet. 2003 Feb 8;361(9356):512-9.

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, et al
The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus.
Diabetes Obes Metab. 2012 Feb;14(2):112-20.

Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ
Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.
PLoS One. 2012;7(4):e35240. doi: 10.1371/journal.pone.0035240. Epub 2012 Apr 10.

Macfarlane S, Macfarlane GT.
Regulation of short-chain fatty acid production.
Proc Nutr Soc. 2003 Feb;62(1):67-72.

MacFarlane, George T. and McBain, Andrew J. (2010). The Human Colonic Microbiota. In Colonic Microbiota, Nutrition and Health. Glenn Gibson, Ed. Dordrecht, the Netherlands: Kluwer Academic Publishers; pp 1-25

Martin FP, Dumas ME, Wang Y, Legido-Quigley C, Yap IK, Tang H, Zirah S, Murphy GM, et al
A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model.
Mol Syst Biol. 2007;3:112.

Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, et al
Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.
Mol Syst Biol. 2008;4:157.

Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S.
Host-gut microbiota metabolic interactions.
Science. 2012 Jun 8;336(6086):1262-7.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Omaida C. Velázquez MD, Howard M. Lederer MD, Dr. John L. Rombeau MD
Butyrate and the colonocyte
Digestive Diseases and Sciences. April 1996, Volume 41, Issue 4, pp 727-739

Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, et al
Prebiotic effects: metabolic and health benefits.
Br J Nutr. 2010 Aug;104 Suppl 2:S1-63.

Schwiertz A, Gruhl B, Löbnitz M, Michel P, Radke M, Blaut M.
Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants.
Pediatr Res. 2003 Sep;54(3):393-9. Epub 2003 Jun 4.

Scott KP, Duncan SH, Louis P, Flint HJ.
Nutritional influences on the gut microbiota and the consequences for gastrointestinal health.
Biochem Soc Trans. 2011 Aug;39(4):1073-8.

Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH.
The influence of diet on the gut microbiota.
Pharmacol Res. 2012 Nov 9. pii: S1043-6618(12)00207-1.

Soret R, Chevalier J, De Coppet P, Poupeau G, Derkinderen P, Segain JP, Neunlist M.
Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.
Gastroenterology. 2010 May;138(5):1772-82.

Tsai F, Coyle WJ.
The microbiome and obesity: is obesity linked to our gut flora?
Curr Gastroenterol Rep. 2009 Aug;11(4):307-13.

Vedantam G, Hecht DW.
Antibiotics and anaerobes of gut origin.
Curr Opin Microbiol. 2003 Oct;6(5):457-61.

Yin L, Laevsky G, Giardina C.
Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity.
J Biol Chem. 2001 Nov 30;276(48):44641-6. Epub 2001 Sep 25.

Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TD, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S.
Destructive effects of butyrate on the cell envelope of Helicobacter pylori.
J Med Microbiol. 2012 Apr;61(Pt 4):582-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Bacteria And The Brain

brain-gears

They’re called flora. Their name comes from the Roman goddess of plants, flowers and fertility, and refers to the plant life occurring in a particular region. The region in this case is the intestine, and the florae that occupy it are micro-organisms that total almost a hundred trillion, a number considerably larger than the number of cells in the human body. So phenomenal are the metabolic activities of these bacteria that they are considered an organ (O’Hara, 2006). Gut bacteria are so influential that they affect more than just a few bodily functions, from immunity to weight control to behavior and concentration (Bravo, 2011). And without them we couldn’t make biotin, vitamin K, or the short-chain fatty acids that energize intestinal cells. An absence of intestinal bacteria is associated with reduction in mucus cell turnover, muscle wall thickness, cytokine production (regulatory proteins), and of course, digestion. The micro-organism population begins in the mouth, where about two hundred different kinds live. They bypass the almost-sterile stomach and then increase on their way to the colon, where several hundred species thrive (Canny, 2008). For all that we know about the body, this area is not completely understood.

Gut diversity is more pronounced in adults than in children and, once developed, tends to remain stable unless dietary changes are dramatic. Generally, those who consume lots of vegetables and fiber have a different composition from those whose diets typify the Western regimens that are high in unwholesome fats and carbohydrates. Studies have demonstrated that what happens in the gut affects what happens in other areas of the body as well, including those that manage mood, anxiety, and possibly the onset of chronic and degenerative diseases (Tillisch, 2013). Suppose we could manipulate intestinal conditions to address health issues, either one at a time or as a group, by using probiotics.

Lactic acid bacteria and Bifidus bacteria are the most common ones used as probiotics, but others may also be employed. The WHO recognizes probiotics as living micro-organisms that confer a health benefit when taken in adequate amounts. The “health benefit,” however, is undefined. What is defined is that specific strains of a beneficent bacteria offer specific effects that cannot be ascribed to other strains, even in the same variety. Therefore, the probiotic used to treat irritable bowel syndrome will be different from the one used for pediatric diarrhea (Verna, 2010). What’s more, the optimal remedial number of colony forming units (CFU’s) for each bacterial strain is still uncertain; and the doses used in animal studies do not necessarily translate to humans. Then there’s the delivery system. Do we use yogurt, milk or a capsule? The gut environs make a difference, too. If too acidic or alkaline, some bacteria cannot survive.

One micro-organism has shown significant promise as a therapeutic agent in the matter of hypertension. It’s called Lactobacillus helveticus, a bacterium used to add a nutty flavor to American Swiss cheese and to prevent bitterness, although it lends character to other cheeses, including cheddar and various Italian varieties. The name helveticus derives from a Gallic tribe that occupied Switzerland in the first century B.C.

L. helvicus produces a compound called a tripeptide. A peptide consists of two or more amino acids linked end to end, sort of like joining batteries in series (That would be positive to negative in order to increase voltage.)  They always hook up between the oxygen-bearing carbon end of one amino and the nitrogen-bearing end of the other. When you get ten or more amino acids in this parade, it’s called a polypeptide; fifty or more give you a protein. That’s the stuff we’re made from. Some peptides, though, are hormones. The biological synthesis of protein depends on messenger RNA that lives on ribosomes; that of peptides doesn’t. A tripeptide has three amino acids. A familiar one is glutathione, an antioxidant made by the body to shield itself from reactive oxygen species. When L. helveticus is used to make a fermented milk product, it forms a tripeptide called IPP, or isoleucine-proline-proline, which acts like an ACE inhibitor.

Without getting too complicated, an ACE inhibitor deals with angiotensin-converting enzyme, a substance that makes angiotensin, which narrows blood vessels after the lub-dub and consequently raises blood pressure. Most of these drugs end in “-pril,” but have different brand names, such as Univasc, Altace or Vasotec. As with all pharmaceuticals, there are side effects, the most common being a bothersome cough. With L. helveticus there are none.  The Finns realized this after conducting a gold-standard clinical trial—randomized, double-blind, placebo-controlled—in which one hypertensive group received no intervention and the other received 150 milliliters (5 oz.) of L. helveticus fermented milk twice a day for ten weeks. There was a four-point difference in systolic pressure and a two-point difference in diastolic pressure between groups, indicating efficacy of the IPP tripeptide (Jauhiainen, 2005). Though these numbers don’t seem like much, they are, indeed, significant. If you prefer higher numbers, another, earlier, Finnish study reported six point and four point differences (Seppo, 2003). Contributing to this positive outcome is a reduction in the arterial stiffness that contributes to hypertension, particularly as we age. Additional study along these lines found that L. helveticus dairy wrought moderate changes in gene expression in the aorta, which you know to be the main artery leading away from the heart (Ehlers, 2011).

Finland is not the only venue enjoying the anti-hypertensive nature of fermented dairy. The Sant’Orsola-Malpighi University Hospital, in Bologna, Italy, noticed that subjects with high-normal blood pressure experienced a drop in numbers, while those with normal readings were unaffected, which is not a surprise (Cicero, 2010). To make this enterprise even more affable, the Japanese used powdered fermented milk to draw similar results, adding a kind of portability to the protocol (Aihara, 2005).

It’s almost hard to bridle one’s encouragement at the prospect of a hypertension management system based on functional food. A few probiotics already contain the strain: Dr. Stephen Langer’s, Garden of Life, and New Chapter are three. Spectra Probiotic by Integrative Therapeutics is another. Kefir, a probiotic drink available in the supermarket, contains L. helveticus, as well as other beneficent micro-organisms. Be advised not to stop any medications. Just know that any decrease in BP is welcome.

References

Bakken JS.
Fecal bacteriotherapy for recurrent Clostridium difficile infection.
Anaerobe. 2009 Dec;15(6):285-9.

Bornstein JC.
Serotonin in the gut: what does it do?
Front Neurosci. 2012 Feb 6;6:16. doi: 10.3389/fnins.2012.00016. eCollection 2012.

Brandt LJ, Reddy SS.
Fecal microbiota transplantation for recurrent clostridium difficile infection.
J Clin Gastroenterol. 2011 Nov;45 Suppl:S159-67.

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
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5.

Philip W. J. Burnet
Gut bacteria and brain function: The challenges of a growing field
PNAS January 24, 2012 vol. 109 no. 4 E175

Collins SM, Bercik P.
Gut microbiota: Intestinal bacteria influence brain activity in healthy humans.
Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):326-7.

PhD, RD, Ajay Kaul, MBBS, MD, Gary Mawe, PhD, Paul Patterson, PhD, and Nancy E. Jones, PhD
Gastrointestinal Conditions in Children With Autism Spectrum Disorder: Developing a Research Agenda
Pediatrics Vol. 130 No. Supplement 2 November 1, 2012: pp. S160 -S168

Cryan JF, O’Mahony SM.
The microbiome-gut-brain axis: from bowel to behavior.
Neurogastroenterol Motil. 2011 Mar;23(3):187-92.

Cryan JF, Dinan TG.
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.
Nat Rev Neurosci. 2012 Oct;13(10):701-12.

J H Cummings, E W Pomare, W J Branch, C P Naylor, and G T Macfarlane
Short chain fatty acids in human large intestine, portal, hepatic and venous blood.
Gut. 1987 October; 28(10): 1221–1227.

Dinan TG, Stanton C, Cryan JF.
Psychobiotics: A Novel Class of Psychotropic.
Biol Psychiatry. 2013 Jun 8. pii: S0006-3223(13)00408-3.

Dinan TG, Cryan JF.
Melancholic microbes: a link between gut microbiota and depression?
Neurogastroenterol Motil. 2013 Sep;25(9):713-9.

Joël Doré, Magnus Simrén, Lisa Buttle, Francisco Guarner
Hot topics in gut microbiota
United European Gastroenterology Journal October 2013 vol. 1 no. 5 311-318

El-Ansary AK, Al-Daihan SK, El-Gezeery AR.
On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups.
Lipids Health Dis. 2011 Aug 19;10:142.

El-Ansary AK, Ben Bacha A, Kotb M.
Etiology of autistic features: the persisting neurotoxic effects of propionic acid.
J Neuroinflammation. 2012 Apr 24;9:74.

Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, McTeague M, Sandler R, Wexler H, Marlowe EM, Collins MD, Lawson PA, Summanen P, Baysallar M, Tomzynski TJ, Read E, Johnson E, Rolfe R, Nasir P, Shah H, Haake DA, Manning P, Kaul A.
Gastrointestinal microflora studies in late-onset autism.
Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.

Foster JA, McVey Neufeld KA.
Gut-brain axis: how the microbiome influences anxiety and depression.
Trends Neurosci. 2013 May;36(5):305-12.

Gomborone JE, Dewsnap PA, Libby GW, Farthing MJ.
Selective affective biasing in recognition memory in the irritable bowel syndrome.
Gut. 1993 Sep;34(9):1230-3.

MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP.
Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.
Behav Brain Res. 2007 Jan 10;176(1):149-69.

MacFabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP.
Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder.
Behav Brain Res. 2011 Feb 2;217(1):47-54.

Mawe GM, Hoffman JM.
Serotonin signalling in the gut-functions, dysfunctions and therapeutic targets.
Nat Rev Gastroenterol Hepatol. 2013 Aug 27.

Parracho HM, Bingham MO, Gibson GR, McCartney AL.
Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.
J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

Azucena Perez-Burgos, Bingxian Wang, Yu-Kang Mao, Bhavik Mistry, Karen-Anne McVey Neufeld, John Bienenstock, Wolfgang Kunze
Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents
Amer J of Phys – Gastro and Liver Phys. 15 Jan2013; Vol. 304 no. G211-G220

Helen R. Pilcher
Bacteria could aid autistics:Clinical trial will put probiotic bugs to the test.
Nature News. Online; 5 May 2004

Robertson DA, Ray J, Diamond I, Edwards JG.
Personality profile and affective state of patients with inflammatory bowel disease.
Gut. 1989 May;30(5):623-6.

Saulnier DM, Ringel Y, Heyman MB, Foster JA, Bercik P, Shulman RJ, Versalovic J, Verdu EF, Dinan TG, Hecht G, Guarner F.
The intestinal microbiome, probiotics and prebiotics in neurogastroenterology.
Gut Microbes. 2013 Jan-Feb;4(1):17-27

Savard P, Lamarche B, Paradis ME, Thiboutot H, Laurin É, Roy D.
Impact of Bifidobacterium animalis subsp. lactis BB-12 and, Lactobacillus acidophilus LA-5-containing yoghurt, on fecal bacterial counts of healthy adults.
Int J Food Microbiol. 2011 Sep 1;149(1):50-7.

Sepiashvili RI, Balmasova IP, Staurina LN.
Serotonin and its immune and physiological effects
Ross Fiziol Zh Im I M Sechenova. 2013 Jan;99(1):17-32.

Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, Cain DP.
Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism.
Neuropharmacology. 2008 May;54(6):901-11

Patrick M. Smith, Michael R. Howitt, Nicolai Panikov, Monia Michaud, Carey Ann Gallini,
Mohammad Bohlooly-Y, Jonathan N. Glickman, Wendy S. Garret
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis
Science. 2 August 2013; Vol. 341 no. 6145: pp. 569-573

Thomas RH, Meeking MM, Mepham JR, Tichenoff L, Possmayer F, Liu S, MacFabe DF.
The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders.
Journal of Neuroinflammation. 2012; 9: 153.

Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA.
Consumption of fermented milk product with probiotic modulates brain activity.
Gastroenterology. 2013 Jun;144(7):1394-401, 1401.e1-4.

Umu OC, Oostindjer M, Pope PB, Svihus B, Egelandsdal B, Nes IF, Diep DB.
Potential applications of gut microbiota to control human physiology.
Antonie Van Leeuwenhoek. 2013 Aug 23.

von Engelhardt W, Bartels J, Kirschberger S, Meyer zu Düttingdorf HD, Busche R.
Role of short-chain fatty acids in the hind gut.
Vet Q. 1998;20 Suppl 3:S52-9.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Probiotics and Blood Pressure

bloodpressure

Maybe what happens in Las Vegas stays in Las Vegas, but what happens in your gut doesn’t stay in your gut, the place we think of as the processing plant that makes nutrients available for use by the body and wastes available for disposal. That part’s correct, but recent interest in the machinations of the system has researchers looking at its relationship to the brain. That means that some of what happens in the gut goes to your head and bypasses the enteric nervous system (ENS), that part of the body called the second brain. Working autonomously, the enteric nervous system is able to coordinate reflexes while controlling the gastrointestinal activity upon which humans rely. Although it communicates with the brain by way of the vagus nerve, the ENS can work independently through a series of neurons that control peristalsis (churning of intestinal contents) and monitor mechanical, chemical and electrical conditions within the system, such as those involved in enzyme secretion and neurotransmitter manufacture. The neurotransmitters of the gut are the same as those in the central nervous system (CNS): acetylcholine, dopamine and serotonin. In fact, more than ninety percent of the body’s serotonin lies in the gut, where it modulates cells of the immune system (Sepiashvili, 2013) (Mawe, 2013). That’s uncommon knowledge, for sure.

What’s this got to do with the brain? Using functional magnetic resonance imaging (fMRI), scientists at UCLA Medical School found that women who regularly consumed probiotic-rich yogurt showed altered activity of brain regions that control the processing of emotion and sensation. The lead author, Dr. Kirsten Tillisch, M.D., commented that the study is of singular merit because it’s the first to show an interaction between a probiotic and the brain. In this work, healthy women with no GI or psychiatric symptoms ate fermented yogurt containing Bifido-, Lacto-, and Strepto- bacterial strains twice a day for a month, and were compared/contrasted to groups that either abstained from such a dairy product or ate one lacking fermented cultures. Before-and-after fMRI’s measured resting brain activity and brain responses to emotion-recognition tasks. Those are the kind in which you look at an image and determine a person’s mood by his facial expressions. This avenue was taken because a previous relationship between gut flora and affective behavior was realized (Umu, 2013) (Dinan, 2013) (Gomborone, 1993) (Robertson, 1989).

Dr. Tillisch observed brain effects in several areas, including those involved in sensory processing and emotional response. An additional conclusion, practically foregone, is that gut flora composition is directed by what we eat (Tillisch, 2013). It is widely accepted that relatively high fiber diets create a gut environment different from typical Western diets. If the brain can send signals to the gut that make you nauseous in times of mental stress, why can’t the gut send messages to the brain?  Inspection has found that Lactobacillus rhamnosus bacteria, common to many yogurt products, affect GABA levels in the brain (Bravo, 2011). GABA is an inhibitory neurotransmitter that reduces anxiety and depression-related behavior. Whether or not Dr. Tillisch’s work is preliminary to something more definitive makes little difference because interest in this field had been piqued years ago (Robertson, 1989).

Some areas of medical and functional study are rife for contrivance, either of outcomes or numbers or some other elements of scientific reporting. The study of autism and its related spectrum of anomalies are not excused from academic chicanery. However, the gut-brain nexus in the study of cerebral challenges offers a fertile arena for probiotic-central nervous system exploration. That there exist perturbations in the gut flora of autistic individuals is properly recognized (Parracho, 2005) (Finegold, 2002). Moving on this link, researchers have identified the higher levels of “bad bacteria” in the guts of children with autism as a variety of Clostridia, though not necessarily defining a cause-effect relationship, but only an association (Pilcher, 2004). Admittedly, genetic and environmental factors play a role in the etiology of this condition. Nonetheless, it is speculated, with at least a small certainty, that probiotics might allay some symptoms of autism by attenuating the toxic by-products of these ignoble bacteria strains.

Anxiety and depression are comorbidities of functional bowel disorders. In subjects so affected, discordant alterations in GABA receptors were remediated by the administration of Lactobacillus rhamnosus, highlighting the valuable role of bacteria in the bi-directional communication of the gut-brain axis (Bravo, 2011) and hinting that certain micro-organisms can be used to treat stress-related disorders, such as anxiety and depression (Cryan, 2012 and 2011).

A venture into neurogastroenterology is as labyrinthine an exercise as can be imagined, right up there with the Biblical epiphany of being fearfully and wonderfully made, and has prompted a convention of “experts” called the International Scientific Association for Probiotics and Prebiotics (ISAPP). Available data on the role of gut bacteria in brain function ascertain the interaction of this microbiota with the ENS, the CNS, and the neuroendocrine and neuroimmune systems. Mammalian brain development and subsequent adult behavior are likewise affected. This could account for the behavioral abnormalities that occasionally accompany gastrointestinal ailments such as IBS and Crohn’s disease, aside from their discomfort.

Short-chain fatty acids are made in the colon when dietary fiber is fermented. These acids contribute to the integrity of the immune and digestive systems, and to the regulation of intestinal (and other) inflammation (Smith, 2013), but their overexpression can be hazardous to cerebral health because they deplete inhibitory GABA (El-Ansary, 2011). Propionic acid (PA) is the main player in this cranial drama, inciting autistic features (El-Ansary, 2012) by increasing markers of oxidative stress, including lipid peroxidation and concomitant decreases in glutathione. Lactic acid bacteria ameliorate the state by increasing GABA stores, (Bravo, 2011) even in the presence of PA, by virtue of their psychoactive character (Perez-Burgos, 2013). And they control PA production by sequestering the Clostridia responsible for its appearance in the first place.

The potential of gut microflora to fine tune human physiology goes beyond the digestive, cardiovascular and immune systems, now to include the nervous system. The thought of regulating cognitions, behaviors, sensations and emotions with bacteria is more than just enlightening.

References

Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y.
Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension.
J Am Coll Nutr. 2005 Aug;24(4):257-65.

Aleixandre A, Miguel M, Muguerza B.
Peptides with antihypertensive activity from milk and egg proteins.
Nutr Hosp. 2008 Jul-Aug;23(4):313-8.

Boelsma E, Kloek J.
Lactotripeptides and antihypertensive effects: a critical review.
Br J Nutr. 2009 Mar;101(6):776-86.

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
PNAS. September 20, 2011; vol. 108 no. 38: 16050-16055

Geraldine O. Canny and Beth A. McCormick
Bacteria in the Intestine, Helpful Residents or Enemies from Within?
Infect. Immun. August 2008 vol. 76 no. 8 3360-3373

Cicero AF, Rosticci M, Veronesi M, Bacchelli S, Strocchi E, Melegari C, Grandi E, Borghi C.
Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, crossover clinical trial.
J Med Food. 2010 Dec;13(6):1363-8.

Cremonesi P, Chessa S, Castiglioni B.
Genome sequence and analysis of Lactobacillus helveticus.
Front Microbiol. 2013 Jan 11;3:435.

Ehlers PI, Kivimäki AS, Turpeinen AM, Korpela R, Vapaatalo H.
High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension.
Br J Nutr. 2011 Nov;106(9):1353-63.

Gonzalez-Gonzalez C, Gibson T, Jauregi P.
Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20/5.
Int J Food Microbiol. 2013 Oct 15;167(2):131-7.

Jauhiainen T, Vapaatalo H, Poussa T, Kyrönpalo S, Rasmussen M, Korpela R
Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement.
Am J Hypertens. 2005 Dec;18(12 Pt 1):1600-5.

Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT.
The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens.
Int J Mol Sci. 2009 Aug 27;10(9):3755-75.

Minervini F, Algaron F, Rizzello CG, Fox PF, Monnet V, Gobbetti M.
Angiotensin I-converting-enzyme-inhibitory and antibacterial peptides from Lactobacillus helveticus PR4 proteinase-hydrolyzed caseins of milk from six species.
Appl Environ Microbiol. 2003 Sep;69(9):5297-305.

O’Hara AM, Shanahan F.
The gut flora as a forgotten organ.
EMBO Rep. 2006 Jul;7(7):688-93.

Seppo L, Jauhiainen T, Poussa T, Korpela R.
A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects.
Am J Clin Nutr. 2003 Feb;77(2):326-30.

Kirsten Tillisch, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, Sophie Legrain–Raspaud, Beatrice Trotin, Bruce Naliboff, Emeran A. Mayer
Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity
Gastroenterology.

June 2013; Volume 144, Issue 7: 1394-1401.e4

Tuomilehto J, Lindström J, Hyyrynen J, Korpela R, Karhunen ML, Mikkola L, Jauhiainen T, Seppo L, Nissinen A.
Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension.
J Hum Hypertens. 2004 Nov;18(11):795-802.

Verna EC, Lucak S.
Use of probiotics in gastrointestinal disorders: what to recommend?
Therap Adv Gastroenterol. 2010 Sep;3(5):307-19.

Yamamoto N, Takano T.
Antihypertensive peptides derived from milk proteins.
Nahrung. 1999 Jun;43(3):159-64.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Colon and Butyrate: The Colon Beyond Punctuation

crammed-jarQuite a lot of people do not like to share their space. It’s understandable that some are uncomfortable when a conversation, as with a stranger, is carried on nose to nose. In Arab countries, it is offensive to step or lean away during such an encounter. There is, however, an instance where closeness cannot be avoided with the microbiome that occupies not only our space, but also us. The human body holds ten times more microbes than human cells, some on the outside, and others on the inside. The skin, the largest organ of the body, houses a range of microbes that live in distinct communities yet work together to protect us from attack by sickness and disease (Grice, 2009). But our attention here is to those on the inside, the microbiota that weigh up to three pounds and contain tens of trillions of members. There might even be more than a thousand different species, about a third of which are common to most of us. The other two-thirds belong only to you.

Though we have a tailor-made personal microbiome, all perform the same physiological functions and have a direct impact on our health. Besides completing digestion by absorbing water and storing wastes, the gut microbes help to make biotin and vitamin K while fighting aggression from the pathogenic gang of bugs and bolstering the immune system. Each of our gut communities remains stable throughout our lives, unless dietary changes are dramatic. Those who consume lots of vegetables and fiber have a different composition from those who live on fatty meats and simple carbohydrates. What happens in the gut telegraphs to what happens in other areas of the body, including areas that manage mood and possibly the onset of chronic and degenerative diseases (Tillisch, 2013).

The neonatal biome starts to form right after birth, when the digestive tract becomes colonized by micro-organisms that come from the mother and from the environment into which it is born. In about three years the biome becomes stable. To keep it that way, we need to take measures that transcend dietary behavior and the mere swallowing of probiotics as adults. Probiotics are micro-organisms. To analogize, they’re like police whose local precinct needs a workplace conducive to efficiency.  If a probiotic, or any array of gut bacteria for that matter, is to augment or to enhance the native population, it needs a favorable place to work. The problem with the typical Western diet is that we feed the upper GI tract without feeding the gut. One way to do that is with resistant starch, the fermentation of which manufactures short-chain fatty acids, notably butyrate. Butyrate nourishes the gut barrier and helps to prevent inflammation.  Very often, however, dietary intake of resistant starch is insufficient to make enough butyrate to be physiologically significant.

What does butyrate do?  It has powerful effects on several colonic functions, not the least of which is the inhibition of inflammation and carcinogenesis, and the reinforcement of the defenses that fight infection and oxidative stress (Hamer, 2008). Butyrate has partners and precursors in the form of acetates and propionates, likewise made by the bacterial fermentation of resistant starch and fiber.  In the company of acetate, butyrate is reported to protect against diet-induced obesity without causing hypophagia, while propionate may reduce food intake. Unfortunately, there is little understanding why this works (Hua, 2012). What distinguishes one from another?  The number of carbons it holds. Acetic acid has two, propionic acid has three and butyric acid has four. The first of these has the scent of vinegar. Propionic acid is found in sweat; butyric acid in rancid butter and vomit.

Butyrate, joined with calcium, magnesium, potassium, sodium or a combination of these minerals inhibits histone deacetylase enzymes, helping butyric acid to enhance the transcription activity of DNA. Sodium butyrate, for example, has been found to increase lifespan in animal experiments (Zhang, 2009). Of the three short-chain fatty acids mentioned, butyrate is more potent than the others at inhibiting invasive colon cancers (Emenaker, 1998). If this activity of the butyrate molecule has been known since the late 1990’s, why has it not received the publicity that newly-concocted drugs, with their hosts of nasty side effects, have?

The reasons for paying attention to your gut go beyond what you read while seated. Some problems can be attenuated with an occasional laxative, although increasing dietary fiber is a better technique. Even the orange-flavored stuff in the plastic canister, used every day, is an improvement. But a butyrate supplement, despite its pungency, is the best thing going, especially as we get older.

References

Arora T, Sharma R, Frost G.
Propionate. Anti-obesity and satiety enhancing factor?
Appetite. 2011 Apr;56(2):511-5.

Bergman EN.
Energy contributions of volatile fatty acids from the gastrointestinal tract in various species.
Physiol Rev. 1990 Apr;70(2):567-90.

Roberto Berni Canani, Margherita Di Costanzo, Ludovica Leone, Monica Pedata, Rosaria Meli, and Antonio Calignano
Potential beneficial effects of butyrate in intestinal and extraintestinal diseases
World J Gastroenterol. Mar 28, 2011; 17(12): 1519–1528.

Emenaker NJ, Basson MD.
Short chain fatty acids inhibit human (SW1116) colon cancer cell invasion by reducing urokinase plasminogen activator activity and stimulating TIMP-1 and TIMP-2 activities, rather than via MMP modulation.
J Surg Res. 1998 Apr;76(1):41-6.

Galvez J, Rodriguez-Cabezas ME, Zarzuelo A.
Effects of dietary fiber on inflammatory bowel disease.
Mol Nutr Food Res. 2005 Jun;49(6):601-8.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J.
Butyrate improves insulin sensitivity and increases energy expenditure in mice.
Diabetes. 2009 Jul;58(7):1509-17.

Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC; NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Murray PR, Green ED, Turner ML, Segre JA.
Topographical and temporal diversity of the human skin microbiome.
Science. 2009 May 29;324(5931):1190-2.

Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ.
Review article: the role of butyrate on colonic function.
Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.

Hua V. Lin, Andrea Frassetto, Edward J. Kowalik Jr, Andrea R. Nawrocki, Mofei M. Lu,
Jennifer R. Kosinski, James A. Hubert, Daphne Szeto, Xiaorui Yao, Gail Forrest, Donald J. Marsh
Butyrate and Propionate Protect against Diet-Induced Obesity and Regulate Gut Hormones via Free Fatty Acid Receptor 3-Independent Mechanisms
PLoS ONE. April 10, 2012 7(4): e35240. doi:10.1371/journal.pone.0035240

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI.
Human nutrition, the gut microbiome and the immune system.
Nature. 2011 Jun 15;474(7351):327-36. doi: 10.1038/nature10213.

Arya Khosravi, Alberto Y—ez, Jeremy G. Price, Andrew Chow, Miriam Merad, Helen S. Goodridge, Sarkis K. Mazmanian
Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection
Cell Host and Microbe. Volume 15, Issue 3, Pages 374-381 (12 March 2014)

Lewis SJ, Heaton KW.
Increasing butyrate concentration in the distal colon by accelerating intestinal transit.
Gut. 1997 Aug;41(2):245-51.

Mortensen PB, Clausen MR.
Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease.
Scand J Gastroenterol Suppl. 1996;216:132-48.

Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T.
Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):597-604.

Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ.
Colonic health: fermentation and short chain fatty acids.
J Clin Gastroenterol. 2006 Mar;40(3):235-43.

Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, Patel H, Mobbs CV.
Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
PLoS Biol. 2009 Nov;7(11):e1000245.

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