microbio ch24 human microbiome

microbiome

all the microbes “that literally share our body space”

each person harbors a unique set of microbes affected by their environment, diet, medications, and other factors

holobionts

hosts and microbes live together and evolve together

humans cannot live a normal life without their microbial partners

normal microbiota

microbes commonly associated with the human body

development of a stable microbiome

normal community of mutualistic and commensal microbiota begins developing at birth and change as we age

we develop an adultlike community of microbes by age 3

it is important to develop a microbiome rich in diversity

human microbiome project

the common fund’s

national institutes of health

available worldwide

microscopic study of human body

~3000 reference bacterial genomes isolated from human body

complete dataset of bacterial, fungal, viral, and protist community composition

multiple studies, datasets, and online resources

early colonization

e. coli and streptococci establish a reducing environment in the intestinal tract

allow growth of anaerobes bifidobacteria and bacteroidetes

bifidobacteria

found in breastfed babies

can synthesize all amino acids and growth factors from simple carbohydrates

have surface proteins that can bind sugars; fermentation of these sugars provides the infant with calories and lowers the gut pH, limiting growth of certain pathogens

adult human microbiota

relatively stable over time

highly variable from person to person and at different sites within the same person

bacteria common to human skin, intestinal tract, and other mucosal surfaces include 5 major phyla:

• actinobacteria

• bacteroidetes

• firmicutes

• fusobacteria

• proteobacteria

a number of archaea, fungi, and viruses are also present

relative areas of human microbes

hair, mouth, manubrium, gluteal crease, GI tract, vagina, penis, inguinal fold, antecubital fossa, axillary vault, external auditory canal

skin

inhospitable environment

slightly acidic pH

high concentration of NaCl

many areas low in moisture

oily lubricant sebum and antimicrobial peptides in other cases

3 environmental niches: dry (greatest microbial diversity), moist, sebaceous (containing sebum; lowest microbial diversity)

skin bacteria

most found on superficial cells, colonizing dead cells, or closely associated with oil and sweat glands

secretion provide the water, amino acids, urea, electrolytes, and fatty acids that serve as nutrients primarily for resident bacteria such as s. epidermidis

oil glands secrete complex lipids that may be partially degraded by enzymes from certain gram positive bacteria, in particular cutibacterium acnes

acne vulgaris

caused in part by activities of cutibacterium acnes

not clear how c. acnes forms acne

convert lipids secreted by oil glands to unsaturated fatty acids; some fatty acids are volatile and may have a strong odor

respiratory tract

colonized by diverse group of microbes

lower is not as sterile as previously thought

upper respiratory tract

areas closest to environment are colonized by gram positive, lipophilic genera staphylococcus, corynebacterium, and cutibacterium

deeper in the nasal cavity: members of gram positive genera streptococcus and dolosigranulum and gram negative moraxella and haemophilus spp.

oropharynx: most diverse; representatives of the genera neisseria, rothia, veillonella, prevotella, and leptotrichia

home to a diversity of viruses: some of which are pathogenic but may or may not make you ill

lower respiratory tract

difficult to sample without contamination from URT

microbes are introduced principally from the oropharynx but their stay is temporary as they are expelled and replaced by new transients

eye

from birth throughout a human life, small numbers of bacteria are found on the conjunctiva

predominant bacteria is staphylococcus epidermidis

external ear

similar to skin flora, with coagulase-negative staphylococci and corynebacterium spp. predominating

mouth

colonized within hours of birth by microorganisms from surrounding environment

anaerobes (porphyromonas, prevotella, and fusobacterium spp) become dominant die to the anoxic nature of the space between teeth and gums

as teeth grow:

• streptococcus parasanguis and s. mutans attach to enamel surfaces

• s. salivarius attaches to the buccal and gum epithelial surfaces (also found in saliva)

• produce a glycocalyx and various other adherence factors that enable them to attach to oral surfaces

• contribute to formation of dental plaque, caries, gingivitis, and periodontal disease

stomach

most microbes killed by acidic conditions

steptococcus, staphylococcus, lactobacillus, peptostreptococcus spp., and yeasts such as candida spp. can survive in gastric fluid

come microorganisms may survive if they pass through very quickly or if the organisms ingested with food are particularly resistant to gastric pH

duodenum

part of small intestine

contains few mircoorganisms due to stomach acid, bile, and pancreatic secretions

gram positive cocci and rods comprise most of microbiota

jejunum

part of small intestine

enterococcus faecalis, lactobacili, diphtheroids, and the yeast candida albicans

ileum

flora present becoming similar to that in colon

pH becomes more alkaline

anaerobic gram negative bacteria and members of the enterobacteracea family become established

large intestine (colon)

largest microbial population of body

among people living in industrialized nations, genera that appear to be part of the core microbiome include: bacteroides, faecalibacterium, clostridia, prevotella, coprococcus, and ruminococcus

genitourinary tract

kidneys, ureter, and urinary bladder normally free of microbes

distal portions or urethra have few (s. epidermidis, e. faecalis, and corynebacterium spp.)

female genital tract

complex microbiota in state of flux due to menstrual cycle

acid-tolerant lactobacilli predominate

functional core microbiome

those microbes that provide the host with a suite of activities required for health and homeostasis (vitamin K from e. coli and emerging role of microbiota in human behavior)

host metabolism

overweight and obese people have higher relative concentrations of gut bacteria belonging to the phylum Firmicutes compared to bacteria belonging to the phylum Bacteroidetes, along with several other changes in gut microbiota population

many bacteria ferment complex polysaccharides into short-chain fatty acids, some of which promote weight gain

immunity

antibiotics disrupt the gut microbial community

following antibiotics treatment, people are at higher risk of GI tract infections

colonization resistance— based on competitive exclusion

gut brain axis

gut microbiota may affect our central nervous system (CNS)

specific behavioral traits (inquisitiveness, sociability, anxiety, depression) differ when comparing GF mice and conventional mice; influence is heritable

we can predict at least 3 ways the microbiome can influence CNS:

• microbiome effect on the immune system

• via enteric nervous system, connected to the CNS by the vagus nerve which transmits signals to the brain

• through soluble microbial products like short-chain fatty acids

loss of microbiome diversity

leads to dysbiosis and a variety of diseases that involve inflammation

metabolic syndrome

condition characterized by at least 3 of the following:

• large waist circumference

• high blood triglyceride level

• high BP

• elevated low-density lipoprotein and fasting blood glucose levels

associated with chronic, low-level inflammation, and this appears to be linked to the microbiome as explained by a phenomenon known as metabolic endotoxemia

cardiovascular disease

diet consumed includes lots of red meat and high-fat foods

little fiber for but microbes to use to produce anti-inflammatory short-chain fatty acids

promotes growth of a “meat-eating” microbial population that metabolizes L-carnitine and phosphatidylcholine resulting in the production of trimethylamine (TMA)

TMA absorbed into the bloodstream travels to the liver where it is enzymatically oxidized by liver cells to trimethylamine N-oxide, associated with the acceleration of atherosclerosis

cancer

microbes are involved in ~20% of malignancies

certain microbes cause host cells to become cancerous

human viruses and bacterial products alter the host cell cycle to favor proliferation and prevent host cells from repairing DNA damage, thereby increasing mutation rates

bacteria like helicobacter pylori dysregulate host cell cycling

bacteria can be involved in metastasis of tumors to distant sites

many linked to microbes are driven by the inflammatory state associated with dysbiosis

probiotics

live microorganisms, which, when administered in adequate amounts, confer a health benefit to the host

US FDA does not regulate probiotic foods and supplements, so claimed health benefits have not been rigorously tested

synbiotics

foods or supplements that include both a prebiotic and probiotic

prebiotic

a compound added too enhance the colonization and positive health benefits of probiotic microbes