1. Microbiology of the Gastrointestinal Tract

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

3. “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

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

5. epithelial lining mucus peristalsis GI Tract Defenses | general defenses

6. liquid flow lysozyme normal flora GI Tract Defenses | mouth defenses

7. peristalsis liquid flow GI Tract Defenses | esophagus defenses

8. acid GI Tract Defenses | stomach defenses

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

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

11. Normal Flora | mouth anaerobes strep viridans other stuff

15. Hemolysis: Alpha: Almost Beta: Best Gamma: Garbage

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

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

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

20. 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

21. Caries

22. 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

23. Healthy gums

24. Gingivitis

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

26. Plaque

28. 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?

29. Weak attachment

30. Aggregation and plaque formation

31. Acid production and tooth decay

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

35. Streptococcus mutans gram stain

36. 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?

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

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

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

40. Oral candidiasis

42. Esophageal candidiasis

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

44. Candida

48. Candida | diagnosis clinical culture useless smear will show hyphal forms

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

50. Peptic ulcer disease: 500,000 new cases each year. 1 million hospitalized. 6000 die. Annual cost: $6 billion.

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

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

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

55. Nobel Prize, 2005

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

59. www.giantmicrobes.com ulcer plush doll: $5.95

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

62. Helicobacter | features microaerophilic corkscrew motility mucinase urease

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

65. Helicobacter | even more features cagA vacA

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

68. 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?

70. Helicobacter infection gastritis ulcergastritiscarcinomalymphoma What happens after infection?

71. Helicobacter infection gastritis ulcergastritiscarcinomalymphoma What happens after infection?

72. Gastritis

75. Helicobacter infection gastritis ulcer gastritis carcinomalymphoma What happens after infection?

76. Helicobacter infection gastritis ulcer gastritiscarcinomalymphoma What happens after infection?

77. Ulcer

79. Helicobacter infection gastritis ulcergastritis carcinoma lymphoma What happens after infection?

80. Gastric carcinoma

82. Helicobacter infection gastritis atrophy intestinal metaplasia carcinoma dysplasia

83. Helicobacter infection gastritis ulcergastritiscarcinoma lymphoma What happens after infection?

84. MALT lymphoma

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

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

89. Normal gastric mucosa

90. Gastric ulcer

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

93. Helicobacter pylori

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

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

99. Stool Antigen test new cheap fast less accurate

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

101. Why might Helicobacter be good?