role of microbiome in opportunistic infections antibiotic associated colitis
urinary tract infectionpyelonephritis
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Maastricht University (UM)
Biomedical Sciences
BBS3024 (BBS3024)
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Case 1: How to maintain a
healthy microbiome?
KEYWORDS
commensals, opportunists, strict pathogens
role of microbiome in opportunistic infections (antibiotic-associated colitis, bacterial
vaginosis, urinary tract infection/pyelonephritis)
skin microbiome, Staphylococcus epidermidis, Staphylococcus aureus
respiratory tract microbiome
eye & ear microbiome
gastrointestinal tract microbiome (including role of pH, diet, functions of gut
microbiota, and bile acids)
genitourinary tract microbiome
intestinal microbial colonization (including impact of birth mode, infant diet, lifestyle)
intestinal microbial aid in host metabolism (SCFA synthesis, carbohydrates and protein
fermentation, methanogenesis)
colonization resistance
intestinal microbiota and disease (metabolic syndrome, cardiovascular disease, cancer)
prebiotics, probiotics, fecal microbiota transplantation
What is microbiome? (done)
Types of microorganisms
The diverse microbiota living throughout the human body is made up of thousands of microbial taxa
from all three domains of life: Archaea, Bacteria, and Eukarya. Microbial load and functional potency
in different body sites are well distinct and have minimal resemblance at higher taxonomic levels
between the two habitats. The highest microbial load, diversity, and functional potency including
biosynthesis of essential nutrients, chemical modifications of dietary components, and sources of
immunomodulatory molecules, are found in the gut microbiome. However, the inter-individual
diversity and dynamics of the human microbiome in a given body habitat vary greatly over time.
, Function and composition of bacteria according to body
sites
Microbiome refers to all the genes found in one’s microbiota—all the microorganisms that live in and
on an organism. Humans cannot live a normal life without their microbial partners—we are
holobionts: hosts and microbes relying on each other, and importantly, evolving together.
In a healthy human, regardless of age, internal organs and tissues (e.g., brain, blood, cerebrospinal
fluid, muscles) are normally free of microorganisms. Conversely, surface tissues (e.g., skin and
mucous membranes) are constantly in contact with the environment and are colonized by various
microbes. Because bacterial species make up most of the microbiota, they are emphasized over
archaea, fungi, protists, and viruses (including phages) that are also part of the microbial assemblage.
, Skin
The skin surface or epidermis has a slightly acidic pH and a high concentration of sodium chloride.
Some areas lack moisture, whereas others are bathed in the oily lubricant sebum and antimicrobial
peptides (AMPs). It has been estimated that the average adult hosts about 10 10 bacteria in these
different skin microenvironments. Some microorganisms are temporarily present and are typically
unable to multiply on the skin. The skin surface can be divided into three environmental niches: dry,
moist, and sebaceous (containing sebum).
In general, bacterial diversity is greatest at dry sites (e.g., forearms, buttocks, hands), harboring a
mixture of Gram-positive and Gram-negative organisms from the phyla Actinobacteriota,
Bacteroidota, Firmicutes, and Proteobacteria. Moist areas (e.g., umbilicus, underarms, inguinal and
gluteal creases) exhibit less diversity, supporting mostly members of Firmicutes and Actinobacteriota
(e.g., Staphylococcus and Corynebacterium spp., respectively), in addition to low numbers of other
bacteria. The skin surfaces with the lowest bacterial diversity are oily sebaceous sites (e.g., forehead,
behind the ear, and the back), where Cutibacterium (formerly Propionibacterium) spp. and other
Actinobacteriota dominate. Staphylococcus epidermidis has long been known to colonize the skin
(thus the species name) and is generally nonpathogenic, unlike S. aureus, which can cause skin
infections. While historically thought to be just hitching a ride, we now know that S. epidermidis is a
key component of healthy skin. It closely associates with keratinocytes. S. epidermidis modulates
keratinocyte gene expression in at least two ways: by secreting products of fermentation called short
, chain fatty acids (SCFAs) and binding to the pattern recognition receptor TLR-2.
This interaction stimulates keratinocytes to release AMPs that limit infection and inflammation,
thereby promoting wound healing. S. epidermidis also inhibits the growth of would-be pathogens
through a process called bacterial interference. Bacterial interference is the capacity of one species
to impact the activities of another. In the case of S. epidermidis, it produces several molecules: AMPs
called bacteriocins, a protease that degrades adhesins that S. aureus needs to attach to host cells,
and molecules that derail quorum sensing used by other microbes. In addition to targeting S. aureus,
S. epidermidis also helps diminish the inflammatory response to Cutibacterium acnes. These bacteria
usually are harmless; however, they are associated with the skin condition acne vulgaris.
Respiratory tract
The respiratory tract is divided into the upper respiratory tract (URT)—the nostrils (also called nares),
sinuses, pharynx, and oropharynx; and the lower respiratory tract (LRT)—the larynx below the vocal
cords, trachea, bronchi, and lungs. While it has long been understood that the URT is colonized by a
diverse group of microbes, we are only beginning to explore the LRT as a site that is not sterile, as
previously thought.
The regions of the URT closest to the environment are the anterior nares, which like skin include host
cells that produce sebum. Thus like skin, the anterior nares are colonized by the Gram-positive,
lipophilic genera Staphylococcus, Corynebacterium, and Cutibacterium. Here we see the same
interaction between S. epidermidis and S. aureus, which reside in the nares. Deeper into the nasal
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