Most of the immune cells reside in
the GI tissue
Each human is estimated to host at least ... diffrenet species
160
Potentially Beneficial Bacteria (4)
- Bifido/bacterium
- Lacto/bacillus
- Eu/bacterium
- Fuso/bacterium
yellow > production of SCFA
pink> Aid in digestion and antiturmor
Potentially harmful bateria
- Clos/tridia
- Staphylo/coccus
- Pro/teus
- Pesudo/monas aeruginousa
Factors leading gut dysbiosis
- Diet
- stress
- Antibiotics use
- Disease
- Infections
- Change in the enviroment
Gut microbiome is not static
- Changes through live stages
- Daily alterations
-Circadian rhythm
Formula fed babies have changes in the gut microbiome
- reduced levels of Bifidobacteria
- increased Clostridiales
At birth, what factors affect the gut microbiome? and observed the abundance of which bacteria?
- Mode of delivery
- Vegina flora
- Gut microbiota
- high level of Proteobacteria
Clock-controlled genes (CCGs) regulate various aspects of physiology including;
• Metabolism
• Gastrointestinal transit time
• Mucus secretion
• Antimicrobial peptide secretion
• Immune defence
• Intestinal barrier function
Jet lag is associated with a disrupted circadian rhythm that has been shown to impact
• bowel movement
• induce gut microbial dysbiosis
• dysfunctional metabolic homeostasis.
Antibiotics-Driven Gut Microbiome Perturbation in Humans
- Colonic bacteria crash after antibiotic treatment, but numbers recover within a week.
- The diversity of the colonic bacteria take much longer to recover >90 days
- Highly variable responses to antibiotics between individuals
- Alters immunity to vaccines
Why do we not suffer from perpetual chronic GI inflammation?
The enteroendocrine cells produce a mucosa that covers and protects the intestinal wall from the gut microbiome (inner mucus and outer mucus layer, and it contains anti-microbial peptides.
Also there are tight junctions between cells to prevent bacterial translocation
Gastrointestinal perforation symptoms
•Vomiting
•Severe abdominal pain
•Bloody stool
•Hardness of the abdomen
•Nausea
•Fever and chills
Despite improvements in surgical and medical treatments, the overall mortality rate is ..... and the mortality rate of cases that also have diffuse peritonitis is up to ....
overall mortality rate is 30% and the mortality rate of cases that also have diffuse peritonitis is up to 70%
Gastrointestinal perforation cause
- Peptic ulcer
- cancer
- IBD
- colitis
- DD
- Operative complications
- Trauma
How do microbes in the intestine influence the host?
Bad bacteria > Immune suppression
Good bateria > immune activation
SCFA (types, where, active group in the molecule)
- most abundant in the proximal colon
- acetate, butyrate, propionate
- Carboxyl group
NDC examples
- cellulose
- Fructoseoligosaccharides
- Galactoseoligosaccharides
- Pectin
- Xylan
SCFA receptors in the gut
- Gpr41/FFA3
- Gpr43/FFA2
- OR51E2 (Acetate and propionate)
Butyrate functions
- Energy source for epithelial cells
- Activates the inflammasome and
- The release of IL-18, which strengthens intestinal barrier integrity.
- Dampens inflammation
- promotes T regulatory cells within the intestine
- Anti-cancer function ( Increased concentrations of butyrate inhibit HDAC activity and induce apoptosis, reduce proliferation and increase immunogenicity of cancer cells)
Gut axis
- Gut liver axis
- Gut heart axis
- Gut lung axis
- Gut kidney axis
- Gut brain axis
Diseases/conditions associated with the
Gut – Brain Axis
- Pain
- Neurodegenerative diseases
- Obesity
- Addiction
- Eplipsy
- Stroke
- IBS
- Anxiety and stress
- Psychiatric disorders
Patients with COVID-19 showed
- Decreased bacterial diversity
- reduced abundance of SCFA-producing bacteria.
- increased numbers of opportunistic pathogens.
- Dysbiosis persisted for at least 30 days after infection
Potential therapies for COVID 19
- Probiotics and prebiotics
- Faecal microbiota transplant
- Microbiota-derived metabolites
- Engineered symbiotic bacteria
Maintaining healthy gut flora could help patients combat cancer.
- Melanoma patients receiving PD-1 blockade had a greater abundance of “good” bacteria in the guts of responding patients.
- Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity.
Faecal microbiota transplant overcomes resistance to anti-PD-1 therapy
Microbiota modulation promoted the infiltration of dendritic cells into remote tumours, which resulted in the activation of both T helper 1 cells via interleukin-12 (IL-12) and cytotoxic CD8+ T cells.