DIG Exam 3 Microbiota Audia

Microbes possess biochemical pathways to metabolize substrates into a form that is _____ by the human host

useable

Microbes produce compounds that we are ____ to produce for ourselves

unable

Microbes set up a niche that is fiercely competitive, limited for space, and nutrients protecting us from colonization by ______ microbes

pathogenic

Hygiene

Diet

Stress

Antibiotics

Influence our microbiome

Lowest microbial load

Helicobacter pylori in some individuals

Lactobacillus species

Stomach and duodenum

Acid tolerant organisms

Bile salts limit growth

Streptococcus, lactobacillus, Enterobacteriaceae

Alkaline 8-10

Jejunum

Facultative anaerobes

pH 5-7

Reduced bile salts

Mixed facultative and anerobic organisms

Transition to anaerobic environment

Ileum

Densest microbial community

90% flora Bacteroidetes (gram - rods) and firmicutes (gram + rods)

Key species Bacteroides fragilis, Bacteroides thetaiotaomicron

Colon

strictly anaerobic environment

Dest complex carbs
Majo contributor to colonic fermentation and SCFA production

B theraiotaomicorn

B fragilis

Microbiome fermentation of dietary fiber to ____

SCFAs

SCFA, primary energy source of colonocytes; maintains barrier integrity

Butyrate

SCFA, travels to liver; GNG substrate

Propionate

SCFA circulates systemically, influences lipid metabolism

Acetate

Vitamin K, folate, biotin

Vitamin synthesis by microbiome

Deconjugation and transformation, regulates lipid absorption and signals via FXR/TGR5 pathways

Bile acid metabolism by microbiome

Gut flora can contribute up to ____-___% of host daily calories through fermentation of otherwise indigestible carbs

10-15

SCFAs interact with host GPCRs to regulate appetite, insulin sensitivity, and inflammation

Metabolic signaling with microbiome contribute to

Microbiomes promote balanced Th1/Th2/Th17 responses

Commensals

SCFA especially butyrate enhances _____ differentiation in the colon. Critical for dampening inflammation and maintaining mucosal tolerance.

Treg

Stimulates dendritic cells to promote Treg development and IL-10 production

Protects against experimental colitis in animal models

B fragilis polysaccharide A (PSA)

Shaped by microbial interactions, reinforces mucosal barrier defense

Secretory IgA

B fragilis colonization restores IL-10 production in a ____ dependent manner

PSA

Commensals provide molecular signals like PSA to actively _____ mucosal tolerance

induce

IL-10 induction occurs almost exclusively in _____ Tregs

Foxp3

A 67-year-old woman presents to her physician complaining of persistent diarrhea with weight loss, bloating, and excess flatulence (passing gas).  She also mentioned her stools looked ‘greasy’, which the physician knew as a sign that ingested fat was not being absorbed. A blood test revealed the woman’s B12 level was abnormally low. Cultures of fecal specimens failed to detect any typical bacterial pathogens that could cause diarrhea.  What is going on?

Decreased vitamin B12 level and excess fat in the stool suggested the woman had a malabsorption disorder

Possible cause  small intestine bacterial overgrowth disease

Characterized by aspirating fluid from the jejunum and finding abnormally high numbers of facultative and anaerobic bacteria such as Streptococcus, E. coli, Lactobacillus and Bacteroides

Fermentation by these organisms produced the bloating and flatulence  Antibiotic treatment corrected the syndrome

Decreased stomach acidity

Reduced peristalsis

Mucosal damage or atrophy

Causes of SIBO

Bacteroides can deconjugate bile acids; less bile leads to malabsorption of fatty acids because micelles do not form

Deconjugated bile acids also inhibit carbohydrate transporters, so sugars accumulate and bacteria ferment them

Fermentation by these organisms produced the bloating and flatulence

The organic acids make lumen pH acidic which helps induce osmotic diarrhea

Deconjugated bile acids also damage enterocytes, leading to water loss

Series of events for SIBO

Rifaximin (RNA polymerase inhibitor)

Augmentin (Ampicillin + Clavulanic acid cell wall synthesis inhibitor)

SIBO treatment

A 24-year-old man presents with several months of abdominal pain, diarrhea, and weight loss. He describes his stools as loose and occasionally containing blood. On physical examination, there is tenderness in the right lower quadrant. Laboratory studies show an elevated C-reactive protein and anemia. Colonoscopy reveals patchy areas of mucosal ulceration separated by normal-appearing mucosa. Biopsies demonstrate chronic inflammation extending through the bowel wall. Stool cultures are negative for bacterial pathogens.

Inflammatory Bowel Disease (Crohn’s, UC)

Reduced microbial diversity

• IBD patients show decreased overall gut flora diversity

• Reduced protective commensals (e.g., Faecalibacterium prausnitzii)

• Increased pro-inflammatory taxa (e.g., Enterobacteriaceae)

Mechanistic relevance

• Dysbiosis promotes barrier disruption and aberrant immune activation (Th17 > Treg imbalance)

• Dysbiosis contributes to chronic, relapsing inflammation in Crohn’s disease and ulcerative colitis (not caused by an infection)

____ patients show decreased overall gut flora diversity

IBD

Increased pro-inflammatory taxa

Enterobacteriaceae

Reduced protective commensals

Faecalibacterium prausnitzii

Dysbiosis promotes barrier disruption and aberrant immune activation (Th17 > Treg imbalance)

contributes to chronic, relapsing inflammation in Crohn’s disease and ulcerative colitis

Reduced microbial diversity and loss of protective commensals

IBD

Underrepresentation of firmicutes in ____

IBD

Definition: Imbalance in microbial communities that disrupts normal host -microbe symbiosis

Dysbiosis

Altered microbiota can increase energy harvest from diet

Phenotype shown to be transmissible in germ-free mouse models (microbiota transplant)

Obesity and the microbiome

A 42-year-old female presents to the Emergency Department (ED) complaining of passing profuse green-colored loose stools she describes as foul smelling and ‘greasy and bloody’ in appearance. She also complains of frequent cramping and nausea. Patient’s temperature is 104 oF / 40 oC. She reports being treated over the last 2-3 weeks with several different ‘kinds’ of antibiotics as part of a recent surgery but doesn’t recall the specific antibiotics. The patient is admitted and a colonoscopy ordered.

C diff colitis

Antibiotic treatment, especially following surgery, kills off normal intestinal microflora, leaving C. diff to grow unabated

C. diff → toxin → damages and kills host epithelial cells → exudative plaques form on the intestinal wall

The small plaques eventually coalesce to form a large pseudomembrane that can slough off into the intestinal contents

C diff Gram positive spore forming anaerobe

1 to 6 days post antibiotic treatment

Watery Diarrhea

Abdominal cramping

Fever

Leukocytosis

Diarrheas beginning within 3 days after hospitalization

C diff symptoms

Disease precipitated by certain antibiotics to which C. dif is resistant

Clindamycin

Ampicillin/Cephalothin

Fluoroquinolones

C diff is normal microbiota in colon of some people

Causes cytokine release

Chemoattractant for PMNs

Inflammation – Diarrhea (rarely bloody)

C diff enterotoxin TcdA

Cell necrosis

Affects tight junctions

C diff necrotizing toxin TcdB

ELISA to Toxin A, or PCR of stool looking for tox genes

diagnosis for C diff

Remove other antibiotics, then...

Oral Vancomycin or Metronidazole

Oral Rehydration Therapy

Metronidazole- generates ROS, damages DNA (for anaerobic)

Vancomycin inhibits Cell wall synthesis (good for GI localized because it is not absorbed well by the gut)

treatment for c diff

Indication: Recurrent C. difficile infection (after antibiotics fail)

Delivery: colonoscopy, NG tube, capsules (emerging)

Investigational uses: IBD, metabolic syndrome, immune modulation

FMT

Fiber-rich diets support SCFA-producing taxa → promote colonic health and immune tolerance

microbiome modulation

Low-fiber/high-fat diets linked to reduced diversity and pro-inflammatory communities

microbiome modulation

Diet can override microbial composition (e.g., germ-free mice colonized with “obese” microbiota but given a fiber-rich diet resist weight gain)

Microbiome modulation

Examples: Lactobacillus, Bifidobacterium

Shown to reduce risk of antibiotic-associated diarrhea in some Randomized Control Trials (RCTs)

Variable or minimal benefit in IBD or obesity

Efficacy is strain- and condition-specific, not “one size fits all”

Transient colonizers

• Most probiotic strains do not permanently integrate into the gut microbiome

• They pass through the GI tract and decline once supplementation stops

Competition with resident microbiota

• Native communities have established niches; probiotics rarely displace them long-term

Detectable only during active ingestion; levels fall rapidly after discontinuation

Daily intake is needed to maintain probiotic effect — benefits are linked to presence, not permanent colonization

Probiotics