Microbiology of the Gastrointestinal Tract

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

“The digestive system is a microbiologist’s paradise. In health or in disease, the digestive tract is a microbial garden of unsurpassed variety and complexity, and feces is the seed of its creation.” - Schaechter INTRODUCTION

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

epithelial lining mucus peristalsis GI Tract Defenses | general defenses

liquid flow lysozyme normal flora GI Tract Defenses | mouth defenses

peristalsis liquid flow GI Tract Defenses | esophagus defenses

acid GI Tract Defenses | stomach defenses

peristalsis liquid flow epithelial shedding decoy binding sites bile Peyer’s patches, IgA, mucus normal flora GI Tract Defenses | intestine defenses

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

Normal Flora | mouth anaerobes strep viridans other stuff

Hemolysis: Alpha: Almost Beta: Best Gamma: Garbage

Normal Flora | esophagus, stomach, small intestine sparse flora increasing distally

Normal Flora | large intestine tons of bugs! anaerobes gram-negative rods enterococcus spirochetes

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

Dental infections | clinical Infectious disease that causes tooth decay Untreated: pain, tooth loss, spread of infection Risk factors: high-sugar diet, poor oral hygiene, reduced amount of saliva, smoking, periodontal disease Dental Caries

Caries

Dental infections | clinical Infectious disease destroying supporting structures of teeth Most common form: gingivitis Other forms (affecting periodontal membrane and alveolar bone) are more serious Periodontal disease

Healthy gums

Gingivitis

Dental infections | pathogenesis What causes tooth decay? Fermentable sugars Acid-producing bacteria Demineralization + enough time

Plaque

Dental infections | pathogenesis Bugs attach weakly to salivary glycoproteins adsorbed onto the surface of the tooth Bugs make “glucans” from dietary sugar Glucans attach bacteria to each other and to tooth, forming large aggregates How does plaque form?

Weak attachment

Aggregation and plaque formation

Acid production and tooth decay

Dental infections | bugs Streptococcus species mutans sanguis Anaerobes Bacteroides fragilis, melaninogenicus Porphyromonas gingivalis Spirochetes Treponema denticola

Streptococcus mutans gram stain

Dental infections | bugs Present normally in large numbers Produces lots of lactic acid quickly Tolerant to low pH, high sugar concentration Has glycosyl transferase (cell-surface protein) attaches to mucins on tooth surface converts sugar into glucans (part of plaque) Paves the way for entry by other organisms What’s so special about S. mutans?

Dental infections | prevention Less sugar in diet Brush and floss frequently Fluoride Saliva Vaccine? Genetically altered bacteria?

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

Candida | clinical newborns, immunocompromised white plaques with red bases oral cavity danger: spread to esophagus, blood

Oral candidiasis

Esophageal candidiasis

Candida | pathogenesis Candida albicans part of normal flora break in host flora → candida takeover

Candida

Candida | diagnosis clinical culture useless smear will show hyphal forms

Introduction GI defenses Normal flora Mouth and Esophagus Dental infections Candida infection Stomach Helicobacter infection Intestine Food poisoning Non-food-related diarrhea LECTURE OUTLINE

Peptic ulcer disease: 500,000 new cases each year. 1 million hospitalized die. Annual cost: $6 billion.

Peptic ulcer disease: unfavorable balance between gastric acid secretion and mucosal resistance genes, smoking, stress - Harrison’s 10 th edition, 1983

Robin Warren Barry Marshall noted unusual bug in stomach grew the bug (eventually) Marshall ingested the bug …and got gastritis The discovery of Helicobacter

‘Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration’ - Warren and Marshall Lancet 1984 The discovery of Helicobacter

Nobel Prize, 2005

Bug characteristics STOMACH | H. pylori small, curved rod gram-negative related to Campylobacter

ulcer plush doll: $5.95

Helicobacter | epidemiology Fecal-oral transmission US: 50% of adults are infected Third world: virtually all adults infected

Helicobacter | features microaerophilic corkscrew motility mucinase urease

C O NH 2 urease urea NH 3 CO 2 ammonia carbon dioxide

Helicobacter | even more features cagA vacA

TFSS* CagA protein cytokines * Type IV Secretion System free radicals VacA protein holes immobilized T-helper cells

Bugs hide in mucous and attract inflammatory cells Inflammatory cells release toxins but can’t kill bugs easily Host causes damage by continual, ineffective immune response! How does Helicobacter cause ulcers?

Helicobacter infection gastritis ulcergastritiscarcinomalymphoma What happens after infection?

Helicobacter infection gastritis ulcergastritiscarcinomalymphoma What happens after infection?

Gastritis

Helicobacter infection gastritis ulcer gastritis carcinomalymphoma What happens after infection?

Helicobacter infection gastritis ulcer gastritiscarcinomalymphoma What happens after infection?

Ulcer

Helicobacter infection gastritis ulcergastritis carcinoma lymphoma What happens after infection?

Gastric carcinoma

Helicobacter infection gastritis atrophy intestinal metaplasia carcinoma dysplasia

Helicobacter infection gastritis ulcergastritiscarcinoma lymphoma What happens after infection?

MALT lymphoma

Helicobacter | diagnosis lots of tests for H. pylori! consider: purpose (diagnosis or follow-up) invasiveness cost

Endoscopy gold standard guided biopsy three tests: rapid urease testing histology culture

Normal gastric mucosa

Gastric ulcer

C O NH 2 urease urea NH 3 CO 2 ammonia carbon dioxide

Helicobacter pylori

Blood test Detects antibodies to Helicobacter Antibodies can persist for years Useful for initial diagnosis only

Breath test C O NH 2 urease urea NH 3 CO 2 ammonia carbon dioxide * *

Stool Antigen test new cheap fast less accurate

Treatment Helicobacter | treatment need an antibiotic! proton pump inhibitor too maybe some bismuth salts

Why might Helicobacter be good?