5 - Microbiome in ID

Question 1

Define:

The combined genetic material of the microorganisms in a particular environment

Answer 1

MICROBIOME

Question 2

Define:

A condition in which all the forms of life present within an organism can be accounted for.

Typically ________ organisms are GERM FREE

Answer 2

GNOTOBIOSIS

Question 3

Define:

Living with, on, or in another

without injury to either

Answer 3

COMMENSAL

Question 4

Define:

Specialized plant fiber that beneficially nourishes the GOOD bacteria

that is already in the Large bowel or Colon

Answer 4

PRE-BIOTIC

FOOD FOR BACTERIA

Question 5

Define:

• *Introduction of a fecal suspension** derived from a
• *healthy doner –> GI tract of a DISEASED individual**

Answer 5

FMT
Fecal Microbiota Transplantation

Question 6

List major components of the microbiome.

Answer 6

Include:

• Prokaryotes (Bacteria)**+**Viruses (Phage*)**
• *Eukaryotes** = Yeast / Protozoa / Helminth

Microbial DIversity
Diversity between BOTH Body Sites & Individuals

• *GUT MICROBIOTA_ = _NOT as Diverse**
• *ProteoBacteria** / ActinoBacteria / Firmicutes / Bacteriodetes

FUNCTIONAL REDUNDENCY
microbiota that yield SIMILAR proteins/metabolite profiles

Question 7

Gene Diversity

Answer 7

• *Bacteria** = 8-Million genes
• *99% are beneficial** // 1% pathogenic

Fungi = 500k genes

Archaea = 80k genes

Human = 22k genes

Question 8

List the major functions of the microbiome critical for human health.

Answer 8

HOST-MICROBIAL MUTUALISM

Production of Beneficial METABOLITES
Short Chain Fatty Acids = Acetate / Propionate / Butyrate
Secondary Bile Acids / Neurotransmitters
Choline-Derived metabolites

Vitamin Synthesis

RESISTANCE against invading pathogens

Maturation of MUCOSAL IMMUNE SYSTEM & Cells

Question 9

Know the major factors that cause dysbiosis in humans.

MEDICATIONS

Answer 9

Prescription medication effects the microbiome diversity in large human cohorts

Even those that DONT directly effect the GUT

STATINS / ANTIDEPRESSANTS / METFORMIN

Antibiotics w/ MAJOR alterations in Microbiome Composition
B-Lactam / Fluoroquinolonges / Tigecycline / Clinda

Favorable perturbation = Rifaximin

Question 10

Know the major factors that cause dysbiosis in humans.

Disease
↑Th1 ↑Th2 ↑Th17

Health
↑Treg cells

Answer 10

Host Genetics
mutations in NOD2 / IL23R / ATG16L / IGRM

LIFESTYLE
Diet / Stress

Early Colonization
Birth in hospitals –> exposure ot microbes

Medical Practices
VACCINATIONS / Antibiotics

Question 11

Know the rational for fecal microbiota transplant (FMT).

C.DIFF & MICROBIOTA

Answer 11

↓Microbial Diversity (w/ AB use)
= Associated with Severe & recurrent C.DIFF INFECTION

Modifiable Risk Factors:
BROAD SPECTRUM AB’s & PPI’s

RECURRENT CDI
due to the regrowth of vegetative bacteria from SPORES that are resistant to antibiotics
Occurs within 1-2 weeks of completing treatment

Risk Factors for Recurrent CDI:
Age / AB’s / PPI / Renal insufficiency

Question 12

Know the rational for fecal microbiota transplant (FMT).

C.DIFF

Answer 12

RE-INTRODUCE a complete & stable community
of GUT MICROBIAL COMMUNITIES
in order to
Repair or Replace
Disrupted Native Microbiota

Methods:
Nasoduodenal Tube / Colonoscopy / Rectal Enema

Question 13

Know the rational for fecal microbiota transplant (FMT).

REDUCE ANTIMICROBIAL RESISTANCE GENES

Answer 13

AB’s in Agriculture & healthcare
has led to a dramatic INCREASE in
PREVALENCE & INCIDENCEof
ANTIBIOTIC RESISTANT BACTERIA = RESISTOME

Question 14

List the major metabolites of probiotic species.

BIFIDOBACTERIUM

Answer 14

Found in Human & Animal Intestines & Vaginas

• *Strict Anaerobe**
• does NOT like OXYGEN*

ACETIC ACID** + **LACTIC ACID
lactic acids help control pH
+
SECONDARY BILE ACIDS

Question 15

List the major metabolites of probiotic species.

LACTOBACILLUS

Answer 15

In nature, milk & dairy products, human & animal intestines & vaginas
Fermented foods

Facultative Anaerobe

LACTIC ACIDS

SECONDARY BILE ACIDS

Question 16

Know the difference between
probiotics and prebiotics.

Answer 16

Probiotics:
Microorganisms that have HEALTH BENEFITS when consumed

THE SEEDS

PREbiotics
Non-Living / Non-digestable carbohydrates
that stimulate the healthy metabolism of gut microbiota

THE FOOD FOR THE PROBIOTICS / FETILIZER

Question 17

FDA REGULATORY STATUS for
PROBIOTICS

Answer 17

LBP = Live BioTherapeutic Products

FDA’s Center for FOOD SAFETY & APPLIED NUTRITION
oversees the probiotic supplement industry:

•Dietary supplements may make structure/function, nutrient content or approved health claims on their labels or in marketing but not disease claims, i.e., that they can treat, mitigate, cure or prevent disease

Question 18

FDA REGULATORY STATUS for FMT

Answer 18

Human Stool = Biological Agent

• *RCDI**
• *Recurrent C.Diff Infection**
• *does NOT require IND, but is strongly encouraged**

IND required for ANY OTHER INDICATION than RCDI

Question 19

Discuss why there is so much conflicting evidence regarding the use of probiotics for antibiotic associated diarrhea.

Answer 19

Research shows that individuals respond very differently to the same probiotic depending on their diet, genetics, microbiome and other aspects of health

GONE BOTH WAYS

but GENERALLY SAFE

Question 20

Types of Probiotics

Answer 20

Sources = Yogurt & Supplements

LACTIC ACID BACTERIA
LactoBacillus
BifidoBacterium

• *NON-LACTIC ACID BACTERIA**
• *Bacillus**

NON-PATHOGENIC YEAST
SaccharoMyces Boulardii

Question 21

Types of PRE-BIOTICS

•Non-living, non-digestible carbohydrates that stimulate the healthy metabolism of gut microbiota

• Resists metabolism by mammalian enzymes and absorption in upper GI
• Is fermented by intestinal bacteria
• Selectively stimulates growth or activity of intestinal bacteria associated with health.

Answer 21

• *INULIN**
• *FructoOligoSaccharides**

Resistant Starch

Gums

Question 22

Dosage & Use of
PROBIOTICS

Answer 22

Typical dose between 6-9 billion CFUs

Post antibiotic dose 10-15 billion CFUs

Moderately healthy GI tract 1 billion CFUs

Timing = WITH or Directly AFTER a Meal

ADR:
Gas / Bloating / Ab tenderness or Pain