2. Fecal Transplants

Fecal Transplant

transfer of stool or portions of stool from one organism into
the gastrointestinal tract of another

Clostridioides (formally Clostridium) difficile

spore-forming pathogen that can colonize the
large intestine and cause colitis

C. diff transmission

Fecal oral, common in hospitals

Major cofactor of C. diff colitis

is the disruption of normal gut flora, often due to antibiotic use.

Do you get c. diff and clear immediately?

No, relapsing infections are common

Main reason FMTs are effective treatment to C. diff

in part to be due to colonization resistance (i.e., the transplanted microbes colonize the colon, reducing the ability of C. difficile to do so)

Secondary reason FMTs are effective aginst c. diff

microbes in the transplanted material producing bacteriocins that kill C.
difficile.

Bacteriocins

a large class of peptides or proteins that are antibacterial, and they are often encoded within mobile genetic elements (e.g., plasmids)

Importance of donor screening

You want someone healthy and not on meds (no illnesses)

Drawback to FMTs

We dont know how the transplant will affect the processes regulated by the microbiome (immune system, weight gain, energy levels etc)

First-line therapy for C. difficile colitis is two
weeks of oral antibiotics. Unfortunately,
relapsing infections are common, occurring in
about 40% of patients. Which of the following is
a contributing factor in the development of
relapsing infections?

antibiotics have a damaging effect on the gut
microbiome

Are all donor species engrafted in the recipient of a FMT?

No, only a subset

Fecal matter contains about a thousand bacterial species. In simple terms, what can happen to these different species following a FMT?

Some may thrive while others may not engraft or survive in the new environment, so diversity will decrease.

Is FMT the only microbiota transplant that is performed?

No it can be done with the mouth, skin, and genital microbiota as well

Probiotics

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

What are the characteristics of an ideal gut probiotic?

The ability to survive passage through the digestive system
 The ability of adhere to intestinal epithelial cells
 The ability to achieve high concentrations in the GI tract
 Being non-invasive and non-pathogenic
 Being antagonistic to pathogens and/or anti-inflammatory
 Not harboring antibiotic resistance genes

The most extensively studied probiotic

is Lactobacillus rhamnosus GG.

What is so unique about L. rhamnosus GG?

First nonpathogenic bacteria to have a pilus (SpaCBA proteins form pili)

SpaCBA proteins

Specific to L. rhamnosus GG (probiotic) that allows them to bind to mucosal lining in GI tract

How could they show that a protein was responsible for mucus binding?

Compare the genomes to the conserved relative, LC705, to see if they have unique proteins and the unique ability to bind to mucus

How could they show that it was specifically pili that were responsible?

Knockout of SpaCBA proteins and determine if binding still occurs

Bacillus species role in gut

Secrete fengycin which inhibits staph Agr system

Fengycin

is a lipopeptide antibiotic produced by Bacillus species that inhibits Agr quorum sensing in Staphylococcus species.

How does Fengycin work?

inhibits Agr by competing with AIP for AgrC binding

Which of the answers below would be a
bad characteristic for a probiotic?
(1) being immunostimulatory but not
proinflammatory
(2) the ability to adhere to intestinal
epithelial cells and colonize
(3) the absence of antibiotic resistance genes
(4) being antagonistic to pathogens
(5) the ability to be killed by the low pH of
the stomac

he ability to be killed by the low pH of
the stomach

Designer probiotics

created to perform novel therapeutic functions, including
the targeting of diseases such as AIDS

How can designer probiotics target AIDS

by expressing an HIV antigen (Gag) on the surface of L.
lactis that elicits a protective immune response