Digestive System

Gastrointestinal Tract

The gastrointestinal tract consists of eight main segments:

1. Mouth
2. Pharynx
3. Esophagus
4. Small intestine
5. Large intestine
6. Rectum
7. Anus

It is also called the alimentary canal. There are also four accessory glands:

1. Salivary glands
2. Liver
3. Gallbladder
4. Pancreas

Digestion Process

Humans are heterotrophic organisms that ingest premade organic compounds. Digestion starts in the mouth through mastication and saliva production.

Saliva

Saliva contains:

• Lysozyme: Degrades bacterial cell walls, reducing bacteria in the mouth.
• Amylase: Digestive enzymes that digest long-chain carbohydrates.
• Low pH in the stomach: Acts as another defense.

Intestine

The intestine, or gut, has digestive functions and defenses. Bile is an antimicrobial compound that dissolves bacterial membranes and emulsifies fats, aiding in fat digestion. Some bacteria, like E. Coli, resist bile by pumping it out.

• Enterics: Bacteria like E. Coli, salmonella, and shigella that resist bile.
• Mucus: A protective layer lining the esophagus, stomach, and intestine.
• Secretory IgA: Special antibodies in mucus that bind to pathogenic bacteria.

Peristalsis

Peristalsis is the rhythmic contraction of smooth muscle that moves food through the digestive tract. Smooth muscle is not under voluntary control. Peristalsis also evacuates the body of unwanted bacteria. Feces are 75% dead bacteria and 25% undigested remains. There is a constant turnover of bacteria.

GALT

GALT (gut-associated lymphoid tissue) includes phagocytic cells like macrophages and dendritic cells that phagocytize common pathogens.

Microbiome of the Intestine

The digestive system has one of the richest microbiomes in the body. The oral cavity has the highest species diversity, similar to a tropical forest, with many microhabitats, including anaerobic and aerobic parts.

Oral Cavity

Main species include:

• Streptococcus: Non-pathogenic species and Streptococcus mutans, which produces acid and is associated with dental caries.
• Neisseria
• Lactobacillus

Stomach

After the mouth, food goes to the stomach, where there is a significant drop in pH to around $pH = 1$. The number of species decreases from 600 to 200 or less. Encountered species include:

• Bacillus
• Streptococcus
• Proteobacteria (including Helicobacter pylori)

The bacterial numbers are also lower, around $10^3$ due to the stomach acid.

Small and Large Intestine

As we move to the small and large intestines, the number of bacteria increases, reaching $10^{11}$ cells per gram of content, with the majority in the large intestine. The large intestine is essentially a fermentation tank. The diversity of the microbiome in the large intestine increases with a more diverse diet, including items like kimchi, pickles, and sushi.

Accessory Organs

Accessory organs, such as the pancreas, liver, and salivary glands, are sterile and free from resident microbes.

Function of Normal Microbiota

Functions of normal microbiota include:

• Protection through competitive exclusion.
• Priming the immune system to react properly to microbial antigens.
• Aiding in digestion and providing nutrients.
• Fermenting fiber to produce volatile fatty acids like acetic acid and lactic acid.
• Producing vitamin K, which is essential for blood clotting.
• Contributing to a healthy intestinal cardiovascular system by producing trace amounts of hydrogen sulfide.

Oral Microbiome and Diseases

Streptococcus Mutans

Streptococcus mutans produces acid through fermentation. It produces a polymer that forms a mesh around the teeth, facilitating its proximity to the teeth surface. This leads to acid production and the development of dental caries. Virulence factors include adhesion proteins and acid production.

Factors Influencing Caries Development

• Genetic predisposition for sweet taste.
• Saliva strength: Alkaline pH neutralizes acid - ample saliva production can delay caries.
• Enamel strength: Influenced by genetics and fluoride, which strengthens enamel.

Predisposition

Children and older adults are more prone to caries due to a propensity for sweetness. Dental caries involves the weakening of enamel, sometimes reaching the dentin.

Opioid Dermatitis and Necrotizing Ulcerative Gingivitis

Gingivitis is inflammation with swelling, redness, and bleeding between teeth. Progression to periodontitis involves the dissolution of gum tissue, weakening the teeth. Deep involvement can cause bone dissolution and tooth loss. Fusobacterium contributes through inflammation and tissue destruction using proteases. Smokers and people from countries with less advanced dental care are more affected.

Mumps

Mumps is caused by para myxovirus, residing in salivary glands. It is transmitted through droplet contact. Symptoms include inflammation of salivary glands, and in some cases, inflammation of testes, ovaries, breasts, thyroid glands, and brain, leading to sterility in rare cases. It is preventable by the MMR vaccine.

Gastritis and Gastric Ulcers

Gastritis is the inflammation of the stomach, characterized by a sharp burning pain in the abdomen. Peptic ulcers are lesions in the mucosa of the stomach, often caused by Helicobacter pylori. Helicobacter pylori infects half of the world population. Virulence factors include:

• Adhesive proteins
• Urease enzyme, which produces ammonia to neutralize stomach acid.

Treatment involves antibiotics like clobutamycin and transmission occurs via the oral or fecal route. Diagnosis involves oxygen tests, immunologic testing in stool, or a urea breath test.

Diarrhea

Diarrhea is defined as three or more loose stools in a 24-hour period. Transmission of diarrheal infectious agents occurs through contaminated food. In tropical countries, children experience more than 10 episodes per year, with a high mortality rate due to dehydration.

Common Causes

• Norovirus (60%): Most common cause in the United States.
• Salmonella (10%)
• Clostridium perfringens (10%)
• Campylobacter (10%)
• Staphylococcus (5%)

Salmonella leads in mortality rates from gastrointestinal diseases.

Salmonella

Salmonella is an enteric bacterium resistant to bile, classified using H (flagellar), K (capsular), and O (cell wall) antigens. Salmonella ferments glucose with acid and gas, produces hydrogen sulfide, and grows rapidly on lab media. Symptoms include vomiting, watery stool, and fever. It is contracted through contaminated chicken, meat, or eggs. Virulence factors include adherence proteins and a capsule. Death can result from syncytemia or severe dehydration.

Shigella and E. Coli

Shigella dysentery causes shigellosis, with frequent watery stools, fever, abdominal pain, nausea, and bloody diarrhea (dysentery). Shigella forms lesions in the intestine, releases endotoxin, and enterotoxin that damages villi. E. Coli o157:H7 occurs when E. Coli acquires Shigella's enterotoxin gene, leading to kidney failure or death. Antibiotics are not recommended to avoid releasing LPS.

Other E. Coli strains include enterotoxigenic E. Coli, causing traveler's diarrhea.

Vibrocholera

Vibrocholera causes cholera, characterized by fluid loss and a high mortality rate (55-70%) due to dehydration. It produces an exotoxin that disrupts intestinal cells, leading to electrolyte and water loss. It transmits via contaminated water, especially during monsoon months. Treatment involves oral rehydration therapy.

Rotavirus and Norovirus

Rotavirus primarily affects children, causing diarrhea. Norovirus is a common viral cause in adults, transmitted through fecal-oral routes. Symptoms include watery diarrhea, vomiting, and mild fever. No vaccine is available.

Symptoms of most diarrheal diseases start 12-48 hours after consuming contaminated food or water, including nausea, vomiting, and loose stool.

Contracted through leafy greens, oysters, fruits, and veggies (norovirus), undercooked poultry (salmonella), or contaminated water (Vibrocholera). Susceptible groups include children under five, adults over 65, and immunocompromised individuals. Treatment is supportive, with vaccines for rotavirus or cholera, notavirus treatment isn't available.

Foodborne Poisoning

In foodborne poisoning, symptoms occur 4-8 hours after contact with food containing bacterial enterotoxins. Two main toxins are:

• Staphylococcus aureus toxin: Heat-stable enterotoxin.
• Clostridium perfringens toxin: Exotoxin in the small intestine.