L1 | Human Microbiome: Definition and Development

Learning Objectives

• Critical to understand basic concepts: microbiota, microbiome, metagenomics, and metagenome.
• Necessary to recognize the characteristics and development of the microbiota.
• Need to pinpoint the most important microorganisms in the gastrointestinal tract.
• Understand the role of the Microbiome as a therapeutic target.
• Beneficial to identify the characteristics and clinical applications of fecal transplants.

The Human Microbiome

• Located in different places in the human body.
• 100 billion microorganisms which benefit humans, who in turn benefit them:200 g
• Aids the digestion of food, produces vitamins, and protects against colonization by pathogenic microorganisms
• Normal Microbiota exists in blood, the brain, and the lungs.

Defining Microbiota and Microbiome

• Each area of the body contains its own microenvironment and several microorganisms.
• Microbiome represents the full collection of genes of all microbes in the human body.
• Individual microbiome is unique.

Defining Metagenome and Metagenomics

• Metagenome: complex genetic material formed by microbiome and the host.
• Metagenomics: analysis of the genetic material of the bacteria, directly from a sample of the medium under study.

Characteristics of the Human Microbiota

• Individual humans are about 99.9% identical in terms of their host genome.
• Individuals can be 80-90% different from one another in terms of the microbiome of their hands or gut.
• Firmicutes (Bacillus, Listeria, Staphylococcus, Enterococcus, Lactobacillus, Streptococcus) and Bacteroidetes (Flavobacteriia and Porphyromonas) represent the two major microbial phyla.

Development of Microbiota

• Development of microbiota occurs in the uterus, during childbirth, breastfeeding, through childhood and into adulthood.

Factors Affecting Microbiota

• Host genetics, diet, age, and mode of birth affect microbiota.
• Antibiotics, exercise, smoking, and geographical location affect microbiota.

Characterizing the Healthy Human Microbiome

• The NIH funded the Human Microbiome Project (HMP) in 2007.
• Defining the "normal" human adult microbiome and investigating its role in various diseases was a key objective.
• Studies included the oral, skin, vaginal, intestine and nasal/pulmonary areas of 300 healthy volunteers.
• Over 10,000 different microbes were found.
• Considered to be a composite of many different microbiomes.
• Most bacteria exhibit a symbiotic relationship with the host.
• Intrapersonal variation was more significant than interpersonal variation.

Oral Microbiome

• The mouth is one of the most heavily colonized parts of the body.
• Several distinct habitats within the oral cavity support heterogeneous microbial communities which constitute an important link between oral and general health.
• Eruption of teeth is responsible for major successions in the oral microbiota.
• Streptococcus dominates the oral cavity, but other abundant genera include Veillonella, Gamella, Rothia, Fusobacterium, and Neisseria.
• Cardiovascular disease, rheumatoid arthritis (Porphyromonas gingivalis), stroke, inflammatory bowel disease, colorectal cancer, respiratory tract infection, appendicitis, pneumonia and diabetes are concerns.

Gastrointestinal Microbiome

• It is permanent and transient.
• More densely populated with 100 trillions of MO.
• Contains >1110 Bacterias species.
• Includes Bacteroidetes (20%-40%), Firmicutes (30%-50%), Actinobacteria (1%-10%).
• Contains fungi, viruses, eukaryotes (amoebas).

Gastrointestinal Tract Microbiome

• Gl tract is the first and most studied.
• Fecal samples are useful for study.
• Enterotypes define groups of individuals by composition of their gut microbiota.
• Gut microbiota may be stratified, and not continuous, creating much debate in the field.
• Contributes to a variety of human diseases, including cancer and obesity.
• Obese individuals have gut microbiota significantly different from that of lean individuals.
• Host genetics influence gut microbial composition and function.
• Diet can influence the microbiota.
• It is a metabolic organ.
• Transforms the complex polysaccharides of the diet, which the human intestine cannot digest or absorb, into monosaccharides and fatty acids.
• Calories derived from this bacterial digestion constitute about 10% of all the energy humans absorb
• Antibiotics significantly affect the host's innate gut microbiota.

Microbiome and Diseases

• Gastrointestinal diseases: Crohn's disease, celiac disease, Non-alcoholic steatohepatitis and irritable bowel syndrome can occur.
• Autism can occur.
• Autoimmune diseases: multiple sclerosis, DM1, asthma, allergies can occur.
• Metabolic diseases: Obesity and Diabetes can occur.
• Cancer: colorectal

Microbiome as a Therapeutic Target

• Probiotics: Living microorganisms (yeast or bacteria) that in adequate amounts increase the population of the microbiota.
• They regulate intestinal movements, avoiding constipation or diarrhea.
• They favor the production of natural enzymes that activate digestion.
• Examples of probiotics include Lactobacilli acidophilus, Lactobacillus casei, Saccharomyces boulardi, Bifidobacteria bifidum.

Therapeutic targets

• Prebiotics are peptides or carbohydrates that the organism cannot digest, and ferment to feed the beneficial bacteria of the intestine.
• They are considered as functional foods.
• Examples of prebiotics include Frutooligosaccharides, Inulin, Galactooligosaccharides, Lactulose, Oat Fiber, Resistant Starch, and Pectin.
• Synbiotic: A combination of a prebiotic with a probiotic.
• Bifidobacteria with galactooligosaccharides.
• Bifidobacterium with fructooligosaccharides.
• Lactobacillus with lactitol.
• Postbiotics: Inanimate microorganisms and/or their components that confer health benefits.
• Short-chain fatty acids, lipopolysaccharides, exopolysaccharides, enzymes, cell wall fragments, various other metabolites such as vitamins and amino acids.

Fecal Transplant

• Procedure involves collecting fecal matter, or stool, from a tested donor.
• Donor stool is mixed with a saline or other solution, strained, and placed in a patient via colonoscopy, endoscopy, sigmoidoscopy, or enema.
• Used to replace beneficial bacteria that has been killed or suppressed, usually by the use of antibiotics such as Clostridium difficile.
• First documented in the 4th century in China and used for over 100 years in veterinary medicine.
• Utilized sporadically in the U.S. since the 1950's, without much regulation.
• Approved by the FDA on June 17th, 2013.
• Diagnosis: stool DNA test
• Treatment with antibiotics – recurrent infection
• Potential donor requirements: no chronic GI disorders such as inflammatory bowel disease, no recent antibiotic exposure (past six months), and not currently immunocompromised.
• Donors should not have recently traveled to endemic areas.