Allergy Research Group Newsletter September 2009 The

playing high levels of anxiety. However, when rat pups were separated andprovided probiotics, and then returnedto their mothers, their immune systemwas equal to that of their never-separated peers and were no more anxiousthan their non-separated siblings. Thisshows how profoundly important ourgut biota is—to both immunity andThe gut is a locus of many of these cymood. Our microbiota not only livetokines as the majority of our innatewith us, they carry an enormous skillimmune system is in the GI tract. Theset that helps us navigate life, from reliterature on the profound dialoguelease of key nutrients to modulation ofbetween the gut and theour immune system. Webrain is surprisingly roare a giant two-leggedThe gut lining first needs to be maturedbust and at the same time,petri dish, more efficientwoefully under the mainthrough the selective use of probiotics that at keeping our bacterialstream radar.specifically stimulate SIgA, and must then be companions alive thanany other medium onIn a fascinating 2007exposed to key strain specific probiotics.earth. To celebrate thisstudy in Brain, Behavunique ecological nicheior and Immunology, researchers found that when the gut infection, or dysbiosis, there may be they provide a range of immune spereleases molecules signaling local persistently variably elevated cytok- cific effects and help us to safely naviinfection, anxiety is enhanced—most ines. These impact mood in a waxing gate a threatening world of pathogensand antigens.likely through the vagus nerve. The and waning manner.vagus nerve provides a neural highway from the neurons of the gut right How important to our immune health In addition, serotonin levels can beinto the brain. Researchers inoculated are friendly gut bacteria? Immeasur- impaired by chronic gut pathogens.mice with the intestinal bug Campy- ably so. When rat pups were separated Certain pathogens including bacteria,lobacter jejuni, and found that vagal from their mother—causing extreme and viruses favor tryptophan as asensory neurons as well as the hypo- stress—and then reintroduced to their primary fuel source. The body maythalamus, amygdala and other im- moms days later, their immune system recognize that tryptophan starvationportant brain areas associated with was forever altered. They were perma- (through the release of a specializedanxiety and stress were activated. In- nently more sensitized to stress dis- enzyme) is an effective strategy to helpfected animals also showed more cauTissue damage including loss of tolerance/ecologytious behavior. The authors concludethat treating infection and inflammation in the gut may help symptomslike anxiety and depression.Animal studies have supported clinical observations in humans. Whenanimals are injected with moleculesthat stimulate cytokines, they becomelethargic, fatigued, and anorexic. Thisis called “sickness behavior” and isassociated with acute and some typesof chronic infections.In another 2009, randomized, doubleblind study in the European Journal ofClinical Nutrition, 39 patients sufferingfrom chronic fatigue syndrome weregiven either placebo or probiotics. Twomonths of supplementation with probiotics was associated with a significantdecrease in anxiety symptoms (p 0.01,highly significant). In a 2007 study, consumption of yogurt-containing probiotics improved mood. This double blindplacebo controlled trial explored 124 patients and found that mood improved inthose who were initially depressed.How Pathogens Sing the BluesWhen our immune system encounters a gut pathogen, proteins on the4Focus September 2009pathogen’s surface bind to specialized receptors. Inflammatory cytokinechemicals such as IL-1, IL-6 TNFαand the chemokine IL-8 are triggered.These in turn stimulate the inflammatory regulator, NF Kappa B. This isnecessary for an aggressive immuneresponse that will help eradicate thatpathogen. The immune system whenhealthy has a series of checks andbalances to contain the damage andreturn to a neutral state after eradication. But in chronic low-grade gutInfectionActivation of Innate Immune ResponseInnate immune cytokinesAcute phase proteinsChemokinesAdhesion moleculesStressNeuroendocrine FunctionMonoamine MetabolismSynaptic PlasticityRegional Brain ActivityAtypical DepressionActivation of Innate Immune Responses and Atypical Depression

suppress and eliminate that pathogen.However, reduced tryptophan meansreduced levels of the feel-goodneurotransmitter, serotonin. Andprescribing an SSRI in this situationcan mean that increased circulatinglevels of serotonin will go right intothe gut. The majority of serotoninreceptors in the GI tract promoteperistalsis—so, like many on SSRI’s,you may get diarrhea. In turn, theinduction of inflammatory cytokinesin response to increased levels of thepathogen will cause further mindbody disturbance by preventing theuptake of serotonin at the synapsesbecause of inflammatoryenzymatic binding.shown that intestinal bacteria candirectly communicate with the centralnervous system by way of the vagalsensory nerve fibers and the peripheralimmune system. If we understandhow potent a neuro-immune effectprobiotics can have, we can use them ina stepwise fashion to tickle and coax ourimmune system into a state of toleranceand ideal, balanced responsiveness.And because the immune and nervoussystems are intimately entwined, ourbrains will respond as well.Think of probiotics as old friends—gentle protectors and supporters withwill slowly catch up to your naturalborn peers but it may take as long as twoyears. But if you were fed formula, yourgut biota may not be ideal. You may bemore likely to suffer from allergies orimmune-related issues. Add in early andfrequent antibiotic treatment and a dietof pre-biotic deficient, processed foodsand you may now have a gut liningthat was never given the opportunity tomature properly. Your core microbiota,which you will carry through your life, isessentially established by age two but hasremarkable plasticity as well, respondingboth positively and negatively tomedications and probiotics.In treating patients, thefirst thing to do is take acomplete history—back tobirth. It’s very importantto know that early historyduring those formativemonths and years, as it will help guideyour treatment protocol.When used correctly, probiotics amelioratemucosal inflammation in the gut, liver,synovium and brain.Youcanseetheexquisitelycomplexdance of pathogens andthe neuroendocrine andimmune system. The common threadof chronic illness is persistent, lowgrade inflammation and disturbedcytokine patterns. Not medicationsisassociated with a decrease ininflammatory biomarkers.A Little Help from My Friendswhom you began your life’s journey.Your own personal microbiota isyour own symphony, one that beginsthe moment you’re born (actually, itmay even begin before you’re born,since the cord blood of caesareanborn infants carries at least sixteendifferent species of bacteria). It isinfluenced by your diet, medications,your geography, and your genetics.And so we come to probiotics—which by regulating cytokine levelsin the gut, can influence infectionand inflammation throughout thebody, and even help balance brainfunction and mood. In recent years theinterface between neuropsychiatry andgastroenterology has converged intoa new discipline referred to as entericneuroscience. Emerging studies haveIn ideal circumstances, you inherit healthylactobacilli from your mother’s vaginalcanal, and breastfeeding provides youwith immunoglobulins, Bifido speciesand antibodies that help your gut liningmature properly, learning tolerance andbalance. Those first months of your lifemay establish a ‘setpoint’ for immunesusceptibility that is key to health. If youwere born caesarean but breastfed, youHowever, you can’t just take a handfulof probiotic capsules containing variable strains and expect to regain yourhealth. The principle function of a probiotic is as an immune modulator butsome strains increase pro inflammatorycytokines and others increase IL-10, themain immune inflammation controller.I have discovered that in order forprobiotics to work most effectively,the gut lining first needs to be matured through the selective use ofprobiotics that specifically stimulateSIgA (secretory Immunoglubulin A),and must then be exposed to keystrain specific probiotics. SIgA is thegreat, forgotten immunoglobulin,The Three Steps to Successful Use of Probiotics in Depression Establish that your patient is suffering from atypicaldepression (inflammation driven) Examine their levels of SIgA by salivary analysis andcorrecting if required. Use the most effective human derived strains of ‘oldfriends’ to suppress excess inflammatory cytokinesby induction of IL-10 and regulate immune responsesystemically.Remember, you don’t have to be aggressive to bepervasive. You can take a small dose of probiotics thatstay in the gut yet influence the entire body systemically.You do need to be consistent and persistent as it maytake some months to change long term dysbiosis.For more information call 800-545-9960 or visit www.allergyresearchgroup.com5

but I’ve championed it for twentyyears because it is so beneficial to theGI tract. SIgA determines our ability to communicate to our immunesystem exactly what bacteria we areharboring and what to do about it.If you don’t have enough SIgA, youcan consume probiotics forever andnever transfer enough of their relevant information to the appropriateimmune tissues in enough volumeto impact health. SIgA and the Tregulatory family of cells work in acooperative manner to maintain tolerance, yet SIgA requires bacteria inthe mucosal lumen to be stimulated.The use of an anti-inflammatory, SIgA-promoting yeast species can be avaluable adjuvant to optimizing gastrointestinal immune tolerance.body, and the key anti-inflammatory,immunomodulating molecule protecting our mucosa in the mouth,nose, lungs, gut, and vaginal tissue.If you give probiotics in a cavaliermanner to someone who does nothave enough SIgA, you won’t get agood clinical response because ofdiminished immune interpretation.In other words, the immune systemdoes not process information frombacteria and pathogens as effectivelyas it needs to when levels of SIgA arelow. I discovered nearly twenty yearsago that if we can improve an individual’s SIgA status, we will then seea change in how they respond to subsequent probiotics. I measure SIgAfrom a salivary sample, since it’s systemic across mucosal tissues.The Treatment PlanIf SIgA is low, I give Saccharomycesboulardii, which is superb at promotingSIgA and has hundreds of peerreviewed studies demonstrating itssafety and effectiveness. I begin withas little as ¼ capsule in children and½ capsule in adults, because thisprobiotic is very potent. Saccharomycesboulardii helps the body break downcarbohydrates more effectively, reducesgut candida and neutralizes clostridiumdifficile toxins A and B, thus improvingmucosal barrier effectiveness. It alsolowers inflammatory IL-8.The first step is to determine if yourpatient is an atypical depressive.Typical features include: a tendencytowards excessive sleep without feelingrefreshed, cravings for carbohydrates,low energy, a feeling their limbs areheavy, poor response to SSRI’s, moreoften female, and highly sensitized tostress and relationship breakdowns. Ialso do an organic acid urinary profileto look for tryptophan catabolite ratios:Quinolinate/Kynurenate. These aremetabolites of tryptophan that can leadto excitotoxicity and excess stimulationof NMDA receptors (see pp 14, NO/ONOO- A Brief Summary of the Workof Martin Pall, Ph.D.). If a patient hasa reasonably good clinical workupto support a diagnosis of atypicaldepression, and has raised ammonia,quinolinic acid or kynurerine in theurine (all indications of dysbiosis) Iconsider it likely their depression is aGI-mediated immune event. You canalso check their stool for pathogens, ortheir blood for raised levels of cytokinessuch as Il-6, Il-1, IL-4, and TNFα as wellas the anti-inflammatory IL-10. Alsoconsider increased gut permeability asa compounding barrier defect allowingcell particulates (LPS) to triggerinflammatory cytokines.If so, the next step is to do testingto establish levels of SIgA, the predominant immunoglobulin in the6Focus September 2009I may also give a month or two of anutritional product called GarumAmoricum , as this has quite quickeffects in the improvement of moodand sleep and really helps the patientto feel that a change is occurring. Itcan take a couple of months with probiotics getting the dose and timingcorrect to see any change in the pattern of mood and behavior.Once SIgA levels are up, I add in Lactobacillus GG, another probiotic withhundreds of studies demonstratingits benefit. This probiotic is a standoutbecause it is so well studied. No otherprobiotic except Saccharomyces boulardii comes close. LGG is a known inducer of anti-inflammatory cytokinesin humans like IL-10. It also increasesthe production of regulatory T-cells,which help to maintain control overinflammation. LGG is a human-derived strain and I believe using humanstrains (ones that have been isolatedfrom the gut of a healthy human) isimportant because they are well recognized by the innate immune systemreceptors and are efficient at primingimmunoregulation. They will, whenused correctly, ameliorate mucosal inflammation in the gut, liver, synoviumand brain. Both LGG and Saccharomyces boulardii are the best studied andprobably most effective probiotics wehave today.I then also add in other human strainsof lactobacillus and bifido species, aswell as Vitamin D, proteolytic enzymes, and herbs, including, as required; artemisinin, black walnut,olive leaf, TOS-free uña de gato, andoregano to modify bacterial communities and help kill gut pathogens.This approach can work phenomenally well. A recent female patientof mine suffered from classic atypicaldepression after her divorce. She hasreduced her antidepressant medications to 1/5th of her initial dose, hasstarted her own business and has losttwenty-one pounds on this simpleprotocol. I expect that in another halfyear she will be able to discontinueall of her medications and yet remaindepression-free.Go with the GutThe gut influences the brain, and thebrain influences the gut. This bi-directional perspective provides a fertilearea for surprising insights into CNSpathologies that have until now proven highly elusive to effective treatment. Ask yourself—what’s better? Agut reaction or a reasoned response?Instinct or intellect? Or is the answerliterally: what’s the difference?References available cus-NewsletterProbiotics-Can-Shift-Mood-sp-97.html

How Lactobacillus GG was DiscoveredA conversation with Barry Goldin, M.S., Ph.D., Tufts UniversityFocus:Why did yougo on a hunt for a specialprobiotic in the first place?Goldin:In 1985, Dr. Barry Goldin and Dr. MelvinGorbach, M.D. isolated Lactobacillus GGdecided to add LGG to theC. difficile culture and foundout it counteracted thetoxin. So then we gave it topeople who had recurringC. difficile infection, andrelapses were prevented.BothDr.after nine years of research. Since then, itGorbach and I werehas become the best studied probiotic ininterested in colon cancerand the factors that maythe world. Here, Dr. Goldin discusses hisToday LGG is the mostinfluence it. We starteddiscovery and its implications.widely studied probioticlooking at ways to alterin the world, one of thebacteriallyderivedfew for which there is goodbest on all our criteria. In fact, it had acarcinogens in 1974, and weevidenceformedical usefulness.began to study probiotics. We decided morphology that was distinct from allto try and isolate one superior strain the other organisms. It would grow aDo you use it yourself?and our conditions were: good survival white, milky kind of colony. It had thisMy family uses it. I myselfin acid, since the organism has to go very sticky property, which I assumehave a rock solid GI tract. But my wifethrough the gastric barrier; resistance was the result of polysaccharides. Toand daughter use it. My daughterto bile acids since it will confront bile this day nobody has absolutely definedrecently had severe tonsillitis andin the duodenum; antimicrobial ability; the cause of LGG’s stickiness.was miserable with a terrible earacheand the ability to stick to the gutAnd how did you determine and bad sore throat. I took her to theepithelium. LGG is among the stickiest antimicrobial ability?ENT, who prescribed her Clindamycinto date of strains that have been testedIn the conventional and LGG to prevent diarrhea. I lookedby us and others.way. We grew a pathogen out on over at him and said, “Hey, that’s theHow did you determinean agar plate and then put the LGG organism I co-discovered.” She tookstickiness?(or other probiotic) in and if it was the LGG and didn’t get diarrhea.Focus:Goldin:Focus:Goldin:Focus:Goldin:We collected buccalcells from the inside of the cheek involunteers. Basically we used a tonguedepressor and scraped their cheek, thentook those cells, put them on filters,and measured stickiness. We also gotcells from ileostomy patients who’dhad part of their bowel removed, andtested those cells in the same way. Weisolated quite a number of organismsuntil we found LGG, which scored theantimicrobial you’d see a clear areaFocus:around the LGG colony.Are you continuing yourwork on LGG?Focus:Goldin:When you isolated theorganism, did you have any idea howbeneficial it would turn out to be forhuman health?Goldin: We had no idea. By pureserendipity a colleague of ours atTufts, a virologist who had isolated theWe’re studying thecombination of prebiotics and LGGright now, to see if we can increasethe counts or effectiveness of theorganism. We also have a researchstudy looking at how LGG influencesthe gastrointestinal immune system.toxin produced by C. difficile bacteria,For more information call 800-545-9960 or visit www.allergyresearchgroup.com7

Lactobacillus GG: A Potent ImmuneRegulator Effective in Many DisordersNew Research Reveals Probiotic’s Anti-Toxin,Anti-Inflammatory, Immune Boosting PropertiesLactobacillus GG is the most prolifically researched probiotic in theworld—over 400 studies have beenpublished that document its remarkable immune-modulating properties.This unique immunobiotic was isolated from a healthy human in 1985by a team of two Tufts University researchers, Barry Goldin, M.S., Ph.D.and Sherwood L. Gorbach, M.D. Theyspent nearly a decade testing organisms until they discovered one thatwas a potent antimicrobial, survivedstomach and bile acid, and was very,very sticky—it adhered well to the gutmucosa. Naming the organism Lactobacillus GG, after the first initials of theirlast names, Goldin reports that the organism was unique in the “white, almost milky creamy colonies it wouldform, probably because of a polysaccharide in the cell wall.”LGG continues to be studied aroundthe world—from Florida to China, Korea to Germany, Finland to Australia,Boston to Italy. In the last two yearsalone researchers have uncovered newbenefits of this probiotic strain far beyond digestive health, as well as deciphering the mechanisms by whichthis hardy organism inhibits pathogensand their toxins, and helps restore andre-set immune function.colitis with Lactobacillus GG.” Chang,a virologist at Tufts who had recentlyisolated the infamously destructivetoxin of C. difficile—the bacteria thatcauses a devastating and often recurrent diarrhea—gave the super probiotic strain to suffering patients aftera course of antibiotics, and relapseswere prevented.That study was the first proof that thisunique organism could benefit humanhealth. The w

women today. I have arrived at this unusual approach after 26 years of practice as an osteopath, naturopath and clini-cal nutritionist treating over 10,000 patients. I believe many clinicians today consider probiot-ics in the s