EXAM Lecture 17 Flashcards
How does the microbiota contribute to the development of obesity
1.high fat feeding
- expansion of tissues
- change in microbiota function and composition
- abundance, diversity, gene count all changing
- results in DYSBIOSIS - increased permeability of epithelial barrier
- 3 lines of defense (apical junctions, mucus barrier, antimicrobial proteins) all compromised - increased LPS absorption
- LPS crosses epithelial barrier - increased endotoxemia
- high circulating levels of LPS in the blood - inflammation
- low grade, chronic
- inflammatory mediators (big 3 (or 4?)) produced - metabolic disorders
- cancer, hypertension, CVD, T2D (insulin resistance)
Microbial dysbiosis and leaky gut in obesity
obese:
- changes in gut microbiota composition and functions = dysbiosis
- loss of mucus barrier and tight junction protein expression (mucus associated bacteria losing their home)
- increased barrier permeability (leaky gut)
- endotoxemia: LPS crosses barrier and stimulates adipose tissue inflammation, PGN also stimulates host inflammation
endotoxemia and cytokine production
obese mice and humans have higher serum endotoxin (LPS) levels and subsequent production of inflammatory mediators
if you block TLR2/4, it significantly reduces the inflammatory mediator production
contribution of the microbiota to obesity (mice study)
regular mouse WITH microbiota fed HFD will become obese
GF mouse WITHOUT microbiota fed the same HFD will stay lean
transplanting the microbiota from an obese regular mouse to a GF mouse will make it become obese (ADOPTS the donow phenotype)
fecal transplant (distal colon microbiota) from human to mouse
obese donor to lean mouse - becomes obese
lean donor to lean mouse - stays lean
lean microbiota has higher microbial diversity, abundance, and gene count than obese
fecal transplantation in obese humans
the gut microbiota plays a central role in controlling insulin sensitivity
obese donor to obese recipient - no change in insulin sensitivity
lean donor to obese recipient - RESTORED insulin sensitivity
Microbiota composition in obesity
gut microbiota changes in response to HFD:
increased abundance of Firmicutes (not every time)
reduced abundance of Bacteriodetes
- Bifidobacterium species (obesity, T2D)
- Faecalibacterium prausnitzii (T2D)
- BOTH exert anti inflammatory and insulin sensitizing effects in the host
- bacteriodetes abundance will increase again when weight is reduced: this suggests that changes in the microbiota composition are responsive to caloric intake
loss of bacterial richness (diversity) at all taxa levels
- characteristic changes used as biomarkers for microbiota function and obesity severity
Microbiome gene counts are..
another indicator of obesity
LGC: low gene count; low numbers of microbial genes expressed
- indicates that the microbiome is LESS ACTIVE and abcterial functions in the microbiota are altered or lost
HGC: high gene count, high numbers of microbial genes expressed
- indicates fully functional capability of the microbiota and redundancy in functions
more obese people have LGC compared to lean
compared to obese HGC individuals, LGC individuals have less microbial diversity and microbiota activity (non host) which has a negative impact on obesity status (host)
specfically, LGC individuals exhibit:
- more adiposity
- insulin resistance
- dyslipidemia
- increased inflammatory mediator production
How do dietary components influence the gut microbiota
average western diet:
- rich in refined foods (high sugar, fat)
- low in fermented foods, complex carbs, fibre
- refined foods are easily broken down in the upper GI tract (thus very little food makes it to colon)
fruits & veggies, whole grains, pulses PROMOTE HEALTH
- phenolic compounds = secondary phenolics
- fibre = SCFA
artificial sweeteners, high fat and sugar PROMOTE DYBIOSIS
= insulin resistance/obesity
food additives can also be damaging
- consumption of artificial sweeteners (aspartame, sucralose, saccharin) drives development of glucose intolerance through alteration of intestinal microbiota
