Lecture 17: Microbial diseases of the digestive systemEdith Porter, M.D.

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Structure & function and normal microbiota of the digestive system

Bacterial diseases Mouth: dental caries, periodontal disease Lower digestive system: peptic ulcer disease, food poisoning,

cholera, gastroenteritis, salmonellosis, typhoid fever, C. difficile antibiotic associated diarrhea

Viral diseases Mumps, gastroenteritis, hepatitis

Fungal diseases Ergot and aflatoxin poisoning

Protozoan diseases Giardiasis, cryptosporidiosis, amoebiasis

Helminthic diseases Tapeworm, pinworm, hookworm, ascariasis, trichinellosis

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>700 species in mouth Viridans

strepotcocci Many anaerobes Spirochaetae No only bacteria

Few in the stomach due to low pH

Few in small intestine due to special defense cells

Large numbers in large intestine, including: Lactobacillus Enterococcus E. coli Enterobacter Klebsiella Proteus Bacteroides

Microbes contribute to ~ 40% of the weight of feces

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Transmitted via food and waterFecal-oral cycle can be broken by:

Proper sewage disposal Disinfection of drinking water Proper food preparation and storage

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Oral bacteria convert sugars to acid

Acid damages tooth enamel

Most cariogenic is S. mutans Biofilm and

subsequently plaque formation

Chewing sugar free gum reduces caries

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Teeth affected, begins on the teeth

Gums affected in-between the teeth Inflammation and degeneration of

structures that support teeth

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Chronic Peptic ulcer caused by H. pylori

Intoxication (food poisoning) caused by ingestion of toxin Symptoms appear 1-48 h after ingestion Treated with fluid and electrolyte replacement

Infection caused by pathogen multiplying in the intestine and producing various toxins Incubation from 12 h to 2 weeks Symptoms usually include diarrhea,

gastroenteritis, dysentery Treated with fluid and electrolyte replacement

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Causes peptic ulcer disease Produces urease (urea

carbon dioxide + ammonia, increases pH), a cytotoxin, and continuously attracts and activates neutrophils

Urease detection used in rapid assays

Treated with antibiotics Chronic H. pylori infection

may lead to stomach cancer

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Staphylococcus aureus enterotoxin is a superantigen

In intestine, it acts as neurotoxin

Nausea, vomiting

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Food poisoningUndercooked rice Ingestion of bacterial exotoxin

produces mild symptoms

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Caused by Vibrio cholerae serotypes that produce cholera toxin Infection rate higher in individuals with impaired gastric acid

production Toxin causes host cells (enterocytes) to secrete electrolytes and

water 12 – 20 L, rice water stool

Toxin does not destroy the enterocyte, no inflammation and no fever

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Most important genera E. coli Salmonella Shigella Yersinia

Identified biochemically and by serotyping with antisera specific for certain surface structures

Symptoms depend on toxin produced Enterotoxin: cholera like, watery diarrhea (E. coli) Cytotoxin (shiga toxin) bloody diarrhea with

inflammation, fever (E. coli, Shigella) Endotoxin mediated: general inflammation, fever

Dysentery: diarrhea with leukocytes in stool as sign of a severe inflammation, accompanied by fever and possibly blood 15

Refer to surface structures H-antigen is part of flagella O-antigen located on LPS K or Vi- (Samonella) antigen - capsule

High antigenic variability16

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Certain strains produce shiga like toxin

Toxin is resorbed and enters circulation

Bacteria remain in the intestine on top of the cells, not inside

Toxin is transported to small vessel

Microvascular endothelial cell damage Inhibition of protein synthesis Apoptosis Platelet activation

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DiseasedNormal

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Ingested Requires large dose

(105) Sources include

chicken and reptiles like turtles

Salmonella enterica serovars such as S. enterica Typhimurium

Affects small intestine Mortality (<1%) due to

septic shock caused by endotoxin

Systemic in immunocompromised

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Salmonella enterica Typhi Human adapted Low infectious dose (~1000) Enter through small intestine Bacteria routinely spread throughout

body in phagocytes High fever, continued headaches Diarrhea only during 2.. and 3. week

when fever declines 1-3% recovered patients become

chronic carriers, harboring Salmonella in their gallbladder 23

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Human to human

Animal product to human

Two component signal transduction Sensor and response

regulator Type III secretion

apparatus Injects proteins directly

into host cell “Hypodermic needle” Injected proteins cause

host toengulf bacterium, prevent fusion of salmonella vacuole with lysosomes, cause diarrhea 25

Induced uptake and intracellular survival in macrophages and enterocytes

Shigella spp. producing Shiga toxin (cytotoxin)

Affects colon Shiga toxin causes

inflammation and bleeding, diarrhea

Dysentery with leukocytes in stool

Typically no systemic spread

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Y. enterocolitica and Y. pseudotuberculosis

Can reproduce at 4°CUsually transmitted in meat and

milkAssociated with arthritis

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Campylobacter jejuniMicroaerophilic gram negative

rods (not member of enterobacteriacea)

Usually transmitted in cow's milkLinked to Guillian-Barre syndrome,

an autoimmune neurological disorder with temporary paralysis

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C. difficile is part of normal microbiota in large intestine

Proliferates and secretes toxins when patient takes antibiotics

Toxins destroy epithelial cells, induce diarrhea , and attract neutrophils Pseudomembranous enterocolitis

Recently, transmission in hospitals noted

MumpsGastroenteritisHepatitis

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Mumps virus Enters through respiratory

tract Infects parotid glands and

leads to painful swelling and fever

May cause orchitis (infection of the testis that may lead to infertility), even less frequently meningitis, inflammation of ovaries, and pancreatitis

Prevented with MMR vaccine 32

Rotavirus 3 million cases annually 1-2 day incubation, 1

week illness Norovirus

50% of U.S. adults have antibodies

1-2 day incubation. 1-3 day illness

Treated with rehydration

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Inflammation of the liverHepatitis may result from drug or

chemical toxicity, EB virus, CMV, or the Hepatitis viruses

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Giardia Flagellated Duodenal infection, prolonged symptoms, may

interfere with food absorption Duodenal fluid is used for diagnosis

Cryptosporidium Numerous stools, cholera like, weight loss Often in AIDS patients Acid fast cysts in stool are diagnostic

Entamoeba Uptake of cysts with are activated by stomach acid Severe dysentery with bloody diarrhea (E.

histolytica) Amoeba (not cysts) with ingested erythrocytes in

stool is diagnostic37

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MycotoxinsProduced by some fungi

Claviceps purpurea▪ Grows on grains▪ Produces ergot (LSD like)▪ Toxin restricts blood flow to limbs; causes hallucination

Aspergillus flavus▪ Grows on grains▪ Produces aflatoxin▪ Toxin causes liver damage; liver cancer

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Caries is a result from biofilm and plaque formation and acid production due to S. mutans and other bacteria

Differentiate food poisoning with ingestion of preformed toxin from gastroenteritis due to pathogens proliferating in the intestine that may produce enterotoxins (watery diarrhea) or cytotoxins (bloody diarrhea with dystentery)

Food poisoning: enterotoxins from S. aureus, B. cereus Gastroenteritis due to bacterial obligate pathogens

(Salmonella, Shigella, Yersinia, Campylobacter, Cholera); bacterial opportunistic pathogens (some E. coli strains); viruses (Rota virus and Noro virus); protozoa (Giradia, Cryptosporidium, Entamoeba histolytica); helminths

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1) Which of the following statements about salmonellosis is false?A) It is a bacterial infection.B) It requires a large infective dose.C) A healthy carrier state exists.D) The mortality rate is high.E) It is often associated with poultry products.

2) Which of the following feeds on red blood cells?A) Giardia lambliaB) Escherichia coliC) Taenia spp.D) Vibrio parahaemolyticusE) Entamoeba histolytica

3) Most of the normal microbiota of the digestive system are found in theA) Mouth.B) Stomach.C) Small intestine.D) Large intestine.E) C and D.

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