Gut, 1992,33,987-993 PROGRESS REPORT Non-immunological defence mechanisms o f the gut S A Sarker, K G y r Abstract Non-immunological defence mechanisms represent a n important line o f intestinal defence i n addition to humoral and cellular immunity. This review summarises t h e evi- dence f o r t h e role o f t h e non-immunological defence Protective factors that have been amply documented a r e gastric juice, intestinal motility, a n d intestinal flora. Components o f pancreatic juice, lysozyme, an d epithelial cell turnover m a y also be involved. Special attention i s given t o gastric acid, infection with Helicobacter pylon, a nd hypochlorhydria a n d their association with infectious diarrhoea. Epidemic hypochlorhy- dria i s discussed since this increases sensitivity to intestinal infections i n third world countries. TABLE I Non- immunological defence mechanisms Gastric acid Intestinal motility Intestinal microflora Lysozyme Pancreatic secretions Bile Medical Department, Kantonsspital Liestal, University o f Basel, 4410 Liestal, Switzerland A Sarker K Gy r Correspondence t o : Professor K Gyr, Medical Department, Kantonsspital Liestal, University of Basel, 4410 Liestal, Switzerland. Accepted f o r publication 8 October 1991 It is generally accepted that humoral a n d cellular immunity plays a k e y role i n t he defence mechanisms of t h e gut. I n addition, t h e non- immunological defence system (Table I ) repre- sents a n important a n d often first line of defence. I t probably affords sufficient protection, a t least in people living i n developed countries with good hygiene. This could explain observations that infectious bacterial disorders o f t h e gastro- intestinal tract ar e not more frequently observed i n patients with humoral and cell mediated immune deficiency.' I n some instances, patients totally lacking secretory immunoglobulins main- tain a perfectly functioning gut.2 Th e acidity o f t h e stomach, t h e motility of t h e intestine, t h e antibacterial effects o f pancreatic enzymes,3'- t h e normal intestinal flora, lysozyme,6 a n d t h e intestinal secretions ar e a l l effective antimicrobial factors that contribute t o t h e non-specific host defence system. Further- more, normal epithelial cell turnover a n d intestinal motility a c t together t o purge t h e intestinal tract o f harmful micro-organisms. Changes i n t h e non-immunological defence factors ca n lead t o increased susceptibility ofthe host t o infections. F o r example, cholera a n d salmonella infections ar e more common i n achlorhydric patients,78 a n d slowing down t h e intestinal motility with belladonna alkaloids prolongs symptomatic shigellosis.9 Gastric acid Th e roles of gastric acid i n health a n d disease a r e manifold. Firstly, i t facilitates digestion o f dietary nutrients an d augments dietary iron a n d calcium absorption. Secondly, i t acts as a major non-immunological defence factor against exogenous pathogenic micro-organisms, a n d also suppresses colonisation o f t h e proximal bowel b y t h e oropharyngeal a n d faecal flora."102 T he following sections will concentrate o n t he bactericidal activity of gastric acid, clinical con- sequences hypochlorhydria, t h e effect o f gastrointestinal infections on gastric acid secre- tion, t h e possible effect o f Helicobactor pylori o n acid secretion, the gastric acid barrier i n malnutrition, a n d t h e epidemiology o f hypo- chlorhydria. BACTERICIDAL PROPERTIES OF GASTRIC JUICE T he l o w pH of t he gastric juice (<3.0) is responsible f o r i t s bactericidal properties. Exogenous bacteria introduced into t h e stomach when t h e p H i s less than 3.0 a r e usually des- troyed within 1 5 minutes.'3 This bactericidal activity is retained u p t o p H 4.0. There ar a number of studies that show t he bactericidal activity o f gastric juice invivo. F o r example, intrayastric bacterial counts, which are normally < 1 0 organisms p e r ml,'4 rise t o >105 organisms p e r m l when acidity i s reduced." Neutralisation of acid b y pretreatment with 2 g sodium bicarbonate reduced t h e infective dose o f Vibrio cholerae 10000 fold'6"' i n healthy volun- teers. Infections with cholera were more likely t o occur i n dogs i f t h e bacteria were given together with bicarbonate.'8 Similarly, t h e frequency o f enteric multiplication o f t h e vaccine strain o f Shigella flexneri increases threefold with sodium bicarbonate neutralisation of gastric juice. 19 With Campylobacter jejuni, a higher incidence o f illness was observed i n a group of healthy volunteers when t e organisms were ingested with sodium bicarbonate.20 T h e u s e o f H 2 receptor antagonists a nd proton pump inhibitors (omeprazole) leads to increased intragastric bacterial counts."52' T h e small bowel colonisa- tion after cimetidine therapy i s also considered t o b e related t o reduced gastric acidity d u e t o the drug.22 Gastric alkalisation o f critically i l l patients with Mylanta I I w as found t o b e associ- ated with intragastric bacterial an d fungal colonisation.23 CLINICAL CONSEQUENCES O F HYPOCHLORHYDRIA On e possible serious consequence o f achlor- hydria o r hypochlorhydria w a s suggested b y t h e eminent British gastroenterologist S i r Arthur Hurst in 1934, when h e mentioned the possi- bility that 'bacillary a n d amoebic dysentery 9 8 7 group.bmj.com on September 4, 2011 - Published by gut.bmj.com Downloaded from
