Microbiome Based Probiotics Flashcards
Shaping immune system by probiotics can lead to
Stimulate production of GI hormones
Manipulation of microbiota via passive processes
Hygiene, diet, lifestyle
Hygiene
Sanitary practices shift primary colonizers
Diet
Phylogenetic variations
Lifestyle
Diversity affected by physical activity (more diverse in athletes)
Active processes to manipulate the microbiome
Antibiotics and prebiotics
Antibiotics lead to (4)
Dysbiosis, low diversity, taxonomic richness, and evenness
Gene altering by antibiotics (3)
Decreased SCFA, glycolysis, vitamin production…for bacterial survival
Why antibiotics lead to negative effects
Have chemicals that inhibit specific functions in cell to stress bacteria
Probiotics affect host
Directly or through its products
Probiotics best studied for
Lactobacillus and Bifidobacterium
Monostrain
Only one strain supplied
Multistrain
Several strains of different species/genera and are most products on market
Multistrains may have
Synergistic effects
Examples of multistrain probiotics
VSL#3 and EcologicRTolerance/Syngut
VSL#3 (7)
S. thermophilus, Eubacterium faecium, B. breve, B. infantis, L. acidophilus, L. Plantum, L. casei, L. delbruekii sb. bulgarisus
Syngut/EcologicTolerance (4)
B. lactis, L. acidophilus, L. pantum, L. lactis
Multistrains work in…
Healthy people, not sick
Probiotics isolated from commensal gut bacteria
Can’t be given definition of probiotics until stability, content, and health effects characterised
Select microbes in gut by…
Understanding which microbes are decreased in different diseases (chose that one to restore microbiome)
MAM
Microbial anti-inflammatory molecules
MAM produced by
Faecalibacterium prausnitzii
PSA
Polysaccharide A from Bacteriodes fragilis
Lactocephin
Inhibitor molecule to get NfKb triggering and T-regs stimulated
Lactocephrin produced by
L. paracasei
Next Generation Probiotics
Develop based on epidemiological studies that find associations between specific taxa and progression from health to subclinical and clinical conditions
Next Generation Probiotics (6)
Faecalibacterium prausnitizii, Akkermansia muciniphila, Bacterodies uniformis and B. fragilis, Eubacterium hallii, Clostridium clusters IV, XIVa, XVIII
F. prausnitzii taxonomy
Firmicutes –> Clostridia –> Clostridiales –> Clostridiaceae (cluster IV)
3-5% of fecal bacteria in humans
F. prausnitizii and A. muciniphila
F. prausnitzii benefits
Decreased in CD (and IBS, UC, and colorectal cancer) –> involved in several dysbiosises
Sensor of intestinal health
F. prausnitzii
F. prausnitzii overall mechanism
Inhibit NfkB activation + Induce T-regs + prevent Th17 activation
How F. prausnitzii inhibits NFkB
Block pro-inflammatory stimulus + butyrate production
How F. prausnitzii activates T-regs
Components interact with DCs that can then go to MLN and induce + Transcytosis through M-cells into lymphoid structures + IL-10 produced by APCs
Th17 blocking by F. prausnitzii
IL-10 from APCs block pro-inflammatory stimuli
Akkermansia muciniphila Taxonomy
Verrucomicrobia, Verrucomicrobiae, Verucomicrobiales, Verrucomicrobiaceae
A. muciniphila lower in (5)
Type 2 Diabetes, obesity, intestinal inflammation, liver disease, chronic alcohol consumption
Adapted to a glycan-rich environment
A. muciniphila via mucus degrading enzymes
How to increase A. muciniphila
prebiotic inulin
Mechanism of A. muciniphila decreases
Thin mucus layer –> Tight junction proteins are compromised –> leaky gut so they can pass through –> LPS stimulates hepatic problems, inflammation, insulin resistance
Mechanism of A muciniphila increases
Mucus thickens to strengthen tight junctions (bacteria cannot get through mucus)
25% of our gut microbiota
Bacteroides species (commensals)
Most common Bacteroides isolate
B. fragilis
Roles of B. fragilis
PSA activates T-cells + Development of immune system homeostasis
B. uniformis
Ameliorate metabolic disorders and immunological dysfunction in obese mice
B. uniformis isolation
Originally from healthy baby
Eubacterium hallii
Important anaerobic butyrate producer resident in out gut
Butyrate functions
- Lower mucosal inflammation and oxidation
- Strengthen epithelial barrier function
- Modulate intestinal motility
- Colonocytes energy source
- Produce SCFA from variety of substances
Inter-relationship between…
Bifidobacterium (degrade complex fibers) and Eubacterium hallii (produce butyrate from broken down complex fibers)
Products of Bifidobacterium include
Formate and lactate and acetate