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.

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