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The Role of Gastric Acid in Preventing Foodborne Disease and How

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The Role of Gastric Acid in Preventing Foodborne Disease and How 1292 Journalof Food Protection, Vol. 66, No. 7, 2003, Pages 1292– 1303 Review TheRole ofGastric Acid inPreventing Foodborne Disease and HowBacteria Overcome Acid Conditions † JAMES L.SMITH U.S.Department of Agriculture,Agricultural Research Service, EasternRegional Research Center,600 East Mermaid Lane, Wyndmoor, Pennsylvania19038, USA Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 MS02-392:Received 24October 2002/ Accepted 7February2003 ABSTRACT Thesecretion of hydrochloric acid by the stomach plays an important role in protecting the body against pathogens ingestedwith food or water .Agastric uidpH of 1to2 isdeleterious to many microbial pathogens; however ,theneutralization ofgastric acid by antacids or the inhibition of acid secretion by various drugs may increase the risk of food- or waterborne illnesses.Peptic ulcer disease is often treated by decreasing or eliminating gastric acid secretion, and such treatment blocks theprotective antibacterial action of gastric uid.The majority of pepticulcer disease cases originate from Helicobacterpylori infections.T reatmentof H. pylori–inducedpeptic ulcers with antibiotics reduces the need for drugs that inhibit gastric acid secretionand thereby diminishes the risk of food- and waterborne illness for peptic ulcer disease patients. Many bacterial pathogens,such as Escherichiacoli, Salmonella Typhimurium,and H. pylori, cancircumvent the acid conditions of thestomach bydevelopingadaptive mechanisms that allow these bacteria to survivein acidenvironments. As a consequence,these bacteria cansurvive acidic stomach conditions and pass into the intestinal tract, where they can induce gastroenteritis. Thestomach has a fundamentalrole in killing or in- thegastric mucosal surfaces. The parietal cells deliver H 1 activatingpathogens present in food or water beforethey and Cl2 intocanaliculi, which crisscross the cellular cyto- enterthe intestinal tract. The stomach is a large-capacity plasm.The canaliculi make up an interconnecting system organlocated between the esophagus and the duodenum oflabyrinthinechannels lined by microvilli. The canaliculi andfunctions as a reservoirfor thestorage, mixing, minc- openonto the parietal cell luminal surface to deliver the ing,and partial digestion of food before it moves into the acidsecretions into the gastric gland lumen, and acid is intestinaltract. In addition, the stomach is theprimary site eventuallydelivered to the stomach lumen (42,49, 61). for hydrochloricacid (HCl) secretion (1). GastricHCl en- Theneurotransmitter acetylcholine, the hormone gas- hancesthe absorption of dietary calcium and iron and ac- trin,and the paracrine (hormone-like) histamine are endog- tivatespepsinogen to pepsin, which is involved in the par- enouschemicals that act in concert to stimulateand control tialhydrolysis of proteins (1). Mostimportantly, gastric acidproduction by bindingto parietalcell surface receptors HClis a majordefense mechanism against pathogens that (1,42, 49, 104). Acidsecretion is also dependent on oxy- maybe ingested with food or water (48, 49). Gastricjuice gen,calcium, and cyclic AMP (cAMP) (87–89). The bind- has a pH of #1withHCl levels of 150 to 160 mEq/ liter ingof acetylcholine, histamine, and gastrin to the parietal (5,475to 5,840 mg/ liter),and the stomach produces 1 to2 cellreceptors results in an increasein intracellularcalcium. litersof gastric juice per day (1, 49). Inthis review, the Histamineactivates adenylate cyclase, which catalyzes the roleof gastric acid as an antibacterial agent and the con- synthesisof cAMP from ATP (42,49, 89). Calcium and sequencesof preventing the secretion of or neutralizing the cAMP-dependentprotein kinases are involved in the acti- acidin the stomach with regard to antibacterialactivity and vationof the acid-secreting proton pump (42,84, 87, 112). themechanisms by which bacteria increase their resistance Thebasic mechanisms involved in acid secretion by toacid environments, including that of the stomach, are theparietal cell are presented in Figure 1. Carbon dioxide discussed. diffusesinto the parietal cell from theblood side of thecell 2 1 HCL SECRETION BY THESTOMACH andcombines with water toform HCO 3 and H through thereaction catalyzed by carbonic anhydrase. The bicar- HClis secreted from theparietal cells located in the bonatepasses out of the parietal cells into the blood in gastricglands. These glands open into the gastric pits on 2 2 exchangefor chlorideions via the HCO 3 /Cl exchange protein.Chloride ions are eventually released from thepa- *Authorfor correspondence. Tel: 215-233-6520; Fax: 215-233-6581; rietalcells into the lumen of thegastric gland via a chloride E-mail: [email protected]. †Mentionof abrandor rm name doesnot constitute an endorsement by ionchannel. Hydrogen ions are released into the gastric 1 theU.S. Department ofAgriculture over others of a similar naturenot glandlumen in exchange for K ionsthrough the action of mentioned. the H1/K1-ATPase(i.e., the proton pump). One hydrogen J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1293 scopicallyexerted a killingeffect on Salmonella Typhi and thatthe addition of arti cial saliva containing nitrite to the gastric uidenhanced the killing of the organism. The ex- perimentsreported by Benjamin et al. (11), Dykhuizenet al. (31), McKnightet al. (64), and Xu et al. (120) strongly suggestthat salivary nitrite and the gastric acid of thestom- achact synergistically to inactivate foodborne pathogens priorto the entry of these pathogens into the gastrointes- tinaltract. Archer (2) hasrecently reviewed the role of sal- ivarynitrite potentiation of theantibacterial action of stom- ach acid. NEUTRALIZING GASTRIC ACID OR INHIBITING Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 GASTRIC ACID SECRETION Thereare a numberof ways to reduce gastric acid or inhibitits formation. HCl secreted by the stomach can be neutralizedthrough the oral administration of absorbable FIGURE 1. Mechanismsinvolved in the secretion of HCl bypa- rietalcells. antacidssuch as sodium bicarbonate or calcium carbonate. Nonabsorbableantacids such as aluminum hydroxide or magnesiumhydroxide are also effective in neutralizing ionis exchanged for apotassiumion for eachA TPmole- stomachacid (66). Acidsecretion by the stomach can also culehydrolyzed. The cytosolic K 1 istransported back into becontrolled surgically. V agotomyis the surgical cutting thegastric gland lumen via K 1 ionchannels (42, 49) (Fig. ofcertain branches of the vagus nerve, thereby preventing 1). therelease of acetylcholine,which is apotentstimulator of gastricacid secretion. Another surgical procedure, gastrec- ROLEOF SALIVARY NITRITEIN GASTRIC ACID tomy,the removal of all or part of the stomach, results in ANTIBACTERIAL ACTION alossof the acid-secreting parietal cells (1, 49). Anumberof studies have indicated that acidic gastric Cholinergic(muscarinic) receptor antagonists block juiceis moreeffective in killingbacteria if nitriteis present. gastricsecretion by bindingto theM 1 muscarinicreceptors Themajor sources of nitrite in the human diet are fruits, onpostganglionic neurons to prevent the release of acetyl- vegetables,cereals, and water containingnitrate (29, 64). cholineand its subsequent binding to parietal cells (99). Ingestednitrate is absorbed from thegastrointestinal tract Anticholinergicagents that inhibit acid secretion include intothe circulatory system, and up to 25% of this nitrate atropine,pirenzepine, glycopyrrolate, and propantheline. iseventually concentrated in the salivary glands. Nitrate is Histamine H2 receptorantagonists are competitive and re- thensecreted in the saliva, in which it is reducedto nitrite versibleinhibitors of gastric acid secretion. These com- bymouthbacteria (28,29, 64). Nitriteis mixed with gastric poundsinhibit the binding of histamineat thehistamine H 2 juicewhen saliva is swallowed.The major sources of nitrite receptorsites on the parietal cells (98, 99). Cimetidine,ra- inthe human diet are not foods containing nitrite that was nitidine,famotidine, and nizatidine are histamine H 2 antag- addedduring processing, but foods that naturally contain oniststhat effectively inhibit gastric acid secretion. The nitrate. substitutedbenzimidazoles, omeprazole, and lansoprazole Withthe use of conditions simulating a normalstom- (protonpump inhibitors) prevent gastric acid secretion by ach,Dykhuizen et al. (31) demonstratedthat Salmonella inhibitingthe enzyme H 1K1-ATPase(i.e., the proton Enteritidis, Salmonella Typhimurium,and Yersiniaentero- pump).These compounds are acid-activeprodrugs that colitica were killedafter 30 min of exposure to nutrient noncompetitivelyb indand i rreversiblyi nactivateth e brothacidi ed to pH 2.1 with HCl. Under the same con- ATPaseby binding covalently to two cysteine residues of ditions, Shigellasonnei and Escherichiacoli O157survived the enzyme (88, 98). unlessnitrite was present.The level of bacteria used was Nalin et al. (70), ina studyinvolving volunteers who ca. 107 CFU/ml.In nutrient broth acidi ed to pH 3.0, the ingested Vibriocholerae, foundthat heavy smokers of can- additionof nitrite was necessaryto kill all of the bacteria nabishad decreased levels of stomach acid and were more testedby Dykhuizenet al. (31). Otherworkers showedthat susceptibleto the diarrhea induced by V. cholerae than nitritepresent in nutrient broth acidi ed to a pHof
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