Probiotics and Blood Pressure

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.

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.