Leaky gut, AKA intestinal permeability, is one of the determining factors in diseases of the liver, which should be tolerant of the normal adaptive quantities of lipopolysaccharides (LPS, fragments of Gram-negative bacterial cell walls) that reach it (other parts of the immune system need to be more sensitive to LPS). If too much LPS reaches the liver because the gut barrier is weakened, or if the liver is made over-sensitive to LPS by factors such as steatosis and cholesterol accumulation, LPS activation of TLR4 can set in motion the immune cascades that lead to fibrosis and necrosis.
TLRs are sensors that amongst other things help orchestrate responses to both potential pathogens and symbiotic organisms. Having just had to replace one of the many sensors in my car that keeps the engine in tune and alerts me to problems, I'm thinking that might be an acceptable analogy for now. A defective sensor crippling the engine to alert me to a problem that doesn't exist is a bit like an allergic reaction, maybe.
Gut integrity is modulated by TLR2
Our findings suggest that dietary saturated fat plays a protective role against MCDD-induced steatohepatitis, whereas TLR-2 deficiency exacerbated NASH. The mechanism underlying the response to dietary fat and TLR-2 likely involves altered signalling via the TLR-4 pathway.
TLR2 is activated by saturated fat, inhibited by polyunsaturated fat.
Dietary saturated fat protects against LPS (endotoxin) activation of TLR4 in hepatic immune cells, but different SFAs achieve this in different ways.
Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.
Meaning: Coconut oil MCTs (also found in butter/ghee and palm oil) normalised serum LPS level by repairing gut integrity, whereas cocoa butter protected the liver by enhancing the clearance or detoxification of LPS.
All the Gram(+) strains increased the number of TLR-2+ cells and the Gram(−) strains [increased the number] of the TLR-4+ cells.
So maybe - and this is backed up by other research - for some purposes the viability or resistance or age or condition of a probiotic supplement can be less important than the strains and number of organisms it contains. And yoghurt cooked into meals, which appears to be a common thing in countries where yogurt is a traditional food, with only Western faddists consistently fetishizing rawness, might have its medicinal uses too.
|Lamb baked in yogurt|
Certainly, a probiotic need not make it alive all the way through the digestive tract to influence host immunity, and some of the objections commonly made in "evidence based" criticisms of probiotics are simply not relevant to some important probiotic modes of action.
"The probiotic paradox is that both live and dead cells in probiotic products can generate beneficial biological responses. The action of probiotics could be a dual one. Live probiotic cells influence both the gastrointestinal microflora and the immune response whilst the components of dead cells exert an anti-inflammatory response in the gastrointestinal tract."
So here we have a mixture of strategies to combine to repair a leaky gut and reduce consequent hepatic inflammation;
1) dietary saturated fats of both MCT and long-chain classes
4) viable live probiotic cultures (and prebiotic fibres)
5) killed probiotics, as well as live commensal species that do not easily colonise the gut