Lecture 2

the collective genome (all genes) of the mibrocial species in a given enviornment. When we sequence microbial communites, we are studying the biome.

the collection of living microogranisms (bactereia, fungi, viruses, archaea) nhabiting a specific enviornment, suchas the huma gut. distinct from microbiome, which refers to their genes.

an NIH initiive (2007-2016) that used genomic and metagenomic sequencing to build a comprehensive reference map of the human microbiome in healthy individuals. sampled 15 body site in men and 18 in women, continued aas the integrative HMP (2014-2016), investigating microbiome changes in IBD, prediabetes, and preterm birth.

a DNA-based method for identifying bacterial species by sequencing the 16S ribosomal RNA gene, which varies between species. Acts as a molecular barcode for bacteria. replaced culture-based methods as the standard for cataloging microbial communities, including organisms that cannot be grown in the lab.

a method that sequences all genetic material in a sample (not just 16S rRNA), providing information about the ful gene content and functional potential of microbial community.

the process by which microorganisms establish themsleves in newborns. influenced by mode of delivery: vaginal birth eposes infants to maternal vaginal and fecal microbiota (Lactobacillus, Prevotella), while cesarean delievery results in colonization by skin and hospital enviornment bacteria (staphylococcus, corynebacterium). further shaped by breastfeedining, which provides oligosaccharides that selectivey feed bifidobacterium. the microbiome stablizes to an adult-like pattern by age 2-3.

the variety of different microbial species present in a given enviornment. in the human body, the gut has the highest diversity, the skin has moderate diversity, and the healthy vaginal nmicrobiome has relatively low diversity (dominated by lactobacillus). loss of diversity is associated with disease.

metabolic products (acetate, propionate, butyrate) generated by gut bacteria from dietary fiber fermentation. SCFAs fuel coloncytes, supporting drug absorption, maintain GI health, and regulate inflammation. considered the metabolic currency of the gut microbiome.

a short-chained fatty acid that is the primary energy source for coloncytes (cells lining the colon). produced by bacterial fermentation of dietary giver. supports gut barrier integrity and has anti-inflammatory properties.

the ability of the resident healthy microbiota to prevent colonization by pathogenic organisms. mechanisms include competition for nutrients, secretion of antimicrobial compounds, and immune activation. disrupted by broad spectrum antibiotics, increasing suseptibility to infections such as c.diff.

a state of healthy, balanced microbiota compostion. associated with intact intestinal mucous membrane protection, proper immune stimulation, efficient digestion, and vitamin synthesis.

an imbalance in the composition or function of microbiota. associated with damage to the intestinal epithelium, production of toxic metabolites (ammonia, biogenic amines), weakened immunity, and linked to conditions including IBD, obesity, diabetes, alzheimer's disease, rheumatoid arthritis and cancer

protein complexes between adjacent epithelial cells that seal the gut lining and regulate what passes between cells. a healthy microbiome strengthens tight junctions; disruption increases intestinal permeability

the degree to which substances can pass through the gut wall. increaes permaeability can result from NSAID use, dysbiosis, or disease states (IBD), allowing bacteria and toxins to cross the epithelial barrier.

a condition in which excessive bacteria accumulate in the samll intestine, causing bloating, diarrhea, and malabsorption. can be triggered by PPOs (which raise gastric pH) or motility disorders. treated with non-absorbable antibiotics such as rifaximin.

the study og how the human microiome influences drug disposition, action, and toxicity, examples: eggerthella lenta inactivates digoxin; enterocococcus faecalis converts levodopa before absorption; colonic bacteria activate the prodrug sulfasalazine; akkermansia abundance correlates with anti PD-1 immunotherapy repsonse.

a gut bacterium that inactivates digoxin in the GI tract, reducing bioavalibility. clinically relevant: digoxin levels should be monitored in patients with GI changes or concurrent antibiotic use.

a bacterial enzume produced by colonic anaerobes that cleaves azo bonds. required to convert the prodrug sulfasalazine into its active component, 5-aminosalicylic acid (5-ASA). antibiotic use can reduce this activation

a gut bacterium whose higher abundance is assocaited with improved repsone to anti0PD-1 checkpoint inhibitor immunotherapy (e.g., nivolumab) in cancer patients. antibiotic use before immunotherapy may reduce this bacterium and thereby reduce treatment efficacy.

a group of chronic inflammatory conditions of the GI tract, including crohn's disease and lcerative colitis. associated with significant loss of microbial diversity. treatment increasingly includes microbiome restoration (probiotics, prebiotics, fecal transplants) in addition to immune suppression.

a form of IBD characterized by transmural (full-thickness) inflammation, most commony affecting the ileum. features include cobblestone mucosal appearnaces, fissures, muscle hypertrophy, fat wrapping, and profound loss of microbial diversity. can occur anywhere in the GI tract.

a form of IBD limited to the colon, characterized by disruption of colon-resistant bacteria (e.g., bacteroides), thinning of the mucus barrier, and mucosal ulceration. may benefirt from butyrate supplementation and fecal microbiota transplantation.

a non-digestable food ingrediant (typically dietary fiber or oligosaccharides) that selectively promotes the growth or activity of beneficial gut bacteria. exmaples include inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

a live microorganisms that when, administed in adequate amounds, confers a health benefit on the host. desiriable characterisitcs include acid and bile stability, adherance to intestinal cells, persistence in the GI tract, production of antimicrobial substancesm antagonism against pathogens, safety in clincal use, and clincally validated health effects. important: not all criteria must be met simultaneously, a probiotic does not have to be of human origin (e.g., saccharomyces bouldardii is a yeast) and the most critical reguirement is safety - the organism must not cause harm. examples: lactobacillus rhammosus GG, bifidobacterium infantis 35624, saccharomyces bouldardii.

a produt combining a prebiotic and an probiotic, designed to deliver live beneficial orgnaisms together with a substrate that supports their growth in the gut.

a non-pathogenic yeast (not a bacerium) with the besst studied evidence for preventing antibiotic-associated diarrhea and as adjunct therapy for concurrent c. diff infection. brand name: Florastor. demostrates that effective probiotics do not have to be of human origin.

a probiotic bacterial strain with strong evidence for treating acute infectious diarrheain children and moderate evidence for preventing antibiotic-associated diarrhea in adults. brand name: culturelle.

a probiotic strain with moderate evidence for imporving global symptoms of irratable bowel syndrome (IBS)

a certification from the US pharmacopeia indicating that a dietary supplement or probiotic has been independently tested and verified for identity, potency, purity, and dissolution. reccomneded as a guality indicator when counseling patients on probiotic selection.

the infusion of processed fecal material from healthy donor into the GI tract of a recipient, with the goal of restoring a healthy microbial community. primary indication: recurrent c. diff infection. routes include colonoscopy, enema, nasogastric tube, and oral capsule.

an FDA approved live biotherapeutic product (approved nov. 2022) for recurrent c. diff infectoon. administered rectally. one of the firsst regulated FMT-derived products.

an FDA approved live biotherapeutic product (approved apr. 2023) for recurrent c. diff nfection. administered as oral capsules. relevant to pharmacy dispensing practice as a prescription product.

a biological product ocntaing live orgnaisms (such as bacteria or bacterial spores) that is regulated by the FDA as a prescription therapeutic. distinguished from dietary supplement probiotics by requiring clincal trial evidence and FDA approval. examples; rebyota, vowst.

an enzyme produced by certain bcacteria (e.g., escherichia coli) that confers resistance to most beta-lactam antibiotics. relevant to FMT safety: a 2019 FDA safety alert reported that two immunocompromised patients recieved FMT containing ESBL-prooducing e. coli; one died. this lead to mandatory donor screening for multidrug-resistant organisms.

an anaerobic, spore-forming bacterium that colonizes the colon when normal microbiota is disrupted, most commonly by broad-spectrum antibiotics, causes antibiotic-assocaited diarrhea and pseudomemranous colitis. recurrent infection is the primary indication for FMT and FDA-aprroved live bioterapeutic products.

a bacterium that colonizes the stomach and causes peptic ulcers and gastritis. treated with triple therapy comibing a proton pump inhibitor (PPI) and two antibiotics.

a genus of anaerobic bacteria that is a mjor componet of the healthy colonic microbiotia. can cause abscesses and peritonitis if the gut barrier is breached. required anaerobic antibiotic coverage (e.g., metronidazole) in GI infections. disrupted in ulcerative colitis.