Introduction to the Microbiology of the Gut (Physiology) UNFINISHED

The human microbiome refers to the collection of microbiota and their genomes in the human body

Microbiota include bacteria, archaea, fungi, protozoa, and viruses that colonize our body surfaces

Approximately 70% of total microbes are found in the gut

Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria are the dominant microbial phyla in the gut

There are approximately 100 trillion (10^14) microbial cells in the human body

The gene diversity of the microbiome is estimated to be 3.3 million genes, compared to approximately 22,000 human genes

The mode of delivery (e.g., vaginal birth or cesarean section), mode of feeding (e.g., breastfed or formula-fed infants), antibiotic use, age, and diet are all factors that influence the variability of the human microbiome

We should view ourselves as a composite of microbial and human cells

Our genetic landscape is a summation of the genes embedded in our genome and the collective genomes (‘microbiome’) of our habitat-associated microbial communities

Our metabolic features are an amalgamation of human and microbial attributes

The GI tract is the largest tube running through the body

The GI tract comprises the oral cavity, esophagus, stomach, small intestine, and large intestine

The main function of the GI tract is the digestion of food and absorption of nutrients

The GI tract provides a large surface area of approximately 200 square meters and is rich in nutrients, making it an ideal environment for microbial colonization

The oral cavity includes the mouth, nose, and throat

♡ Prevotella

♡ Porphyromonas

♡ Desulfovibrio

♡ Bacteroides

♡ Fusobacterium

♡ Eubacterium

♡ Peptostreptococcus

♡ The stomach is a J-shaped organ that receives food from the esophagus

♡ It aids in both chemical and mechanical digestion

♡ The low pH of the stomach makes it almost sterile, with fewer than 10^3 colony-forming units (cfu) per milliliter of gastric contents

♡ Microorganisms in the stomach are transient rather than resident

♡ Acid-tolerant lactobacilli

♡ Yeasts

♡ Helicobacter pylori

Helicobacter pylori is a gram-negative bacterium.

Helicobacter pylori colonizes the human stomach in early life

Approximately 50% of the world's population are carriers of H. pylori

♡ Disease occurs in about 15% of carriers and may include peptic ulcers, gastric inflammation (gastritis), and gastric cancer

♡ The small intestine digests and absorbs nutrients.

♡ The small intestine consists of the duodenum (upper part), jejunum, and ileum (lower parts)

♡ Lower numbers of bacteria (~10^3 per gram) are present due to the secretion of bile and short transit time

♡ Higher bacterial numbers (up to 10^7 per gram) are found in the ileum

♡ Enterococci

♡ Enterobacteria

♡ Lactobacilli

♡ Bacteroides

♡ Clostridia

There is a rapid increase in population in the large intestine (colon), with approximately 10^12 microorganisms per gram

♡ The large intestine (colon) provides favorable conditions for microbial growth, including a suitable pH, nutrient availability, and a slow transit time

♡ Bifidobacterium

♡ Bacteroides

♡ Eubacterium

♡ Lactobacillus

The GI tract is sterile at birth.

The GI tract is colonized by microorganisms from the mother and the environment

Early colonizers are aerotolerant as the gut initially contains oxygen; they are later replaced by anaerobes

The gut microbiota stabilizes within the first few years of life

As many as 1000 species can be found in the gut microbiota

The gut microbiota exhibits varying composition and numbers along the length of the GI tract

♡ Mode of delivery: vaginal vs. caesarean section

♡ Diet: breastfed vs. formula fed

♡ Antibiotic use

♡ Age

♡ Environment

♡ Digestion of food

♡ Development of the gut immune system

♡ Production of short-chain fatty acids

♡ Production of essential vitamins

♡ Resistance to colonization by pathogens

Changes or alterations in microbiota (dysbiosis) are associated with various diseases

A reduction in bifidobacteria and an increase in other microbial groups are commonly seen

Altered community profiles of microbiota may be both a cause and a consequence of disease.

While changes in microbiota composition are correlated or associated with disease, it is important to note that correlation does not imply causation

Bifidobacterium are anaerobic, non-motile heterofermentative Gram-positive rods

Bifidobacterium are common inhabitants of the gastrointestinal tract

There are approximately 90 species of Bifidobacterium

The optimum growth conditions for Bifidobacterium are at 37-41°C and pH 6.5-7.0

Bifidobacterium ferment carbohydrates using the fructose-6-phosphate phosphoketolase shunt

Bifidobacterium are predominant in breast-fed infants

The population of bifidobacteria decreases with age, being highest in infancy, declining and remaining stable in adulthood, and further declining in elderly age

Gut microbiota composition can be modulated through dietary interventions such as probiotics and prebiotics

♡ Probiotics

♡ Prebiotics

Faecal microbiota transplantation

Probiotics are live microorganisms that can confer a health benefit when administered in adequate amounts.

Dairy products are the most common vehicles for delivering probiotics.

The most common probiotic strains are members of Lactobacillus and Bifidobacterium

Various health claims are associated with probiotic strains

♡ Prevention of diarrhea

♡ Alleviation of lactose intolerance

♡ Control of inflammatory bowel disease (IBD) and irritable

♡ bowel syndrome (IBS)

♡ Cancer prevention

♡ Cholesterol reduction

♡ Modulation of the immune system

♡ Establishment of healthy microbiota in premature infants

Probiotic benefits may occur directly or indirectly through several mechanisms:

♡ Modulation of the intestinal ecosystem

♡ Improved colonization resistance

♡ Modulation of immune response

The consumption of probiotics and the transient colonization that occurs can influence the composition and activity of the natural gut microbiota, helping to maintain a beneficial balance.

Probiotics increase the population of beneficial bacteria and decrease the population of harmful microorganisms

Probiotics achieve this by producing organic acids or short-chain fatty acids, which lower the gut pH, and by producing antimicrobial agents such as bacteriocins

Probiotics make the gut more favourable to beneficial bacteria such as lactobacilli and bifidobacteria, and consequently, less favourable to pathogenic microorganisms

The growth and metabolism of probiotic microorganisms can alter the intestinal environment, leading to improved colonization resistance

Probiotics may adhere to epithelial cells, blocking the adhesion of pathogens through competitive exclusion. They may also stimulate mucin production, enhancing intestinal barrier function

Probiotics stimulate mucosal immunity and modulate immune responses by interacting with the gut-associated lymphoid tissue (GALT)

The GALT is the largest lymphoid tissue in the human body and contains various cells of the immune system that interact with intestinal microorganisms

Metabolites, cell wall components, and DNA of probiotic microorganisms are recognized by host cells sensitive to them, such as toll-like receptors

Activation of toll-like receptors leads to modulation of pro- and anti-inflammatory cytokine expression, resulting in downregulation of inflammatory and allergic responses

Very few health claims related to probiotics have been approved due to unsatisfactory dossiers of evidence to back such health claims

Many manufacturers now favor the use of descriptors such as 'beneficial bacteria', 'live bacteria', and 'good bacteria'.

The term 'probiotic' implies health benefit and is therefore subject to scrutiny

Prebiotics are substrates that are selectively utilized by host microorganisms, conferring a health benefit

The criteria for a compound to be considered a prebiotic include being resistant to gastric acidity, hydrolysis by enzymes, and gastrointestinal absorption, as well as being fermented by intestinal microbiota and selectively stimulating the growth and/or activity of intestinal bacteria associated with health and wellbeing.

Examples of prebiotic compounds include inulin, fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylo-oligosaccharides (XOS), isomaltooligosaccharides (IMO), soybean oligosaccharides (SOS), mannanooligosaccharides (MOS), lactosucrose, lactulose, human milk oligosaccharides (HMOs), conjugated linoleic acid (CLA), polyunsaturated fatty acids (PUFAs), and plant polyphenols.

Natural sources of prebiotics include agave, banana, garlic, onions, leeks, Jerusalem artichoke, chicory, and wheat

Bifidobacteria predominates the microbiota found in breast-fed infants compared to formula-fed infants.

Human breast milk contains bifidogenic factors such as lactulose, N-acetyl-glucosamine-containing saccharides, and human milk oligosaccharides (HMOs), including short-chain trisaccharides and complex, high-molecular-weight glycans.

HMOs, which are only partially digested in the small intestine, reach the colon where they selectively stimulate the development of bifidobacteria in the gut microbiota.

FMT stands for Faecal Microbiota Transplantation, and its purpose is to administer a solution of faecal matter from a donor into the intestinal tract of a recipient to directly change the recipient’s microbial composition and confer a health benefit.

♡ Conditions for which FMT is used include:

♡ C. difficile infection

♡ Irritable bowel syndrome (IBS)

♡ Inflammatory bowel disease (IBD)

♡ Ulcerative colitis

♡ Crohn’s disease

Some terms used to describe gastrointestinal tract infections include:

♡ Gastroenteritis

♡ Diarrhoea

♡ Dysentery

♡ Enterocolitis

Gastroenteritis is an acute syndrome characterized by gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and abdominal discomfort, typically caused by an infection.

Diarrhoea is defined as watery or liquid stools, often accompanied by an increase in stool weight above 200 g per day and an increase in daily stool frequency, along with a sense of urgency. It can lead to severe dehydration, excessive fluid and electrolyte loss, organ failure, long-term morbidity, and reduced growth.

Dysentery is an inflammatory disorder of the gastrointestinal tract, typically affecting the large intestine. It is often associated with the presence of blood and pus in the feces, along with symptoms such as pain, fever, and abdominal cramps.

Enterocolitis refers to inflammation involving the mucosa of both the small and large intestine.

Escherichia coli:

♡ ETEC (Enterotoxigenic E. coli)

♡ EPEC (Enteropathogenic E. coli)

♡ EIEC (Enteroinvasive E. coli)

♡ EHEC (Enterohaemorrhagic E. coli)

♡ Salmonella

♡ Campylobacter

♡ Vibrio cholerae

♡ Shigella

♡ Noroviruses

♡ Rotaviruses

♡ Astroviruses

Bacterial toxins can exert pharmacological actions locally or at distant sites, as seen in cholera infections.

Superficial microbial invasion triggers local inflammation, evident in conditions like Shigella dysentery or Campylobacter food poisoning.

Deep invasion leads to dissemination of organisms to other body sites, causing conditions such as enteric fevers like Typhoid fever or Hepatitis A

Perforation or ulceration may lead to serious conditions like peritonitis or intra-abdominal abscesses, as observed in infections like those caused by Entamoeba

Bacterial toxins, such as enterotoxins, affect the gut by altering fluid and electrolyte transport, leading to diarrhoea.