Organoid-derived adult human colonic epithelium responds to co-culture with a probiotic strain of Bifidobacterium longum

General Discussion
#1

This might be a pretty advanced way to look at this.
Again, retinoic acid metabolism might be a key regulatory feature of this strain.
Commensal bacteria might regulate vitamin a metabolism and storage.
Unfortunately this is one of the most expensive and unstable probiotics on the market.
its also not even available at the higher dosage of 5 billion per capsule outside of the states.

Organoid-derived adult human colonic epithelium responds to co-culture with a probiotic strain of Bifidobacterium longum


In germ-free animals the lack of microbes within the gut results in a propensity to mucosal inflammation among other immune deficits. This suggests microbes are essential for the healthy function of the human gut, but we have lacked a reproducible mechanistic model of interactions between human colonic epithelium and the anaerobic microbes within the gut. To establish the physiological effect of a common anaerobe in the human gut, we co-cultured a probiotic strain of Bifidobacterium longum (35624) with organoid-derived adult human colonic epithelium in asymmetric gas conditions (anoxic apically, 5% oxygen basolaterally) and compared to axenic (‘germ-free’) epithelium. Bacteria proliferated and retained their normal cellular morphology in the presence of the human colonic epithelium. The human colonic mucosa retained trans-epithelial electrical resistance (TEER) consistent with an intact epithelium but lower than in axenic conditions. Changes in TEER corresponded to changes in Claudin-family gene expression. Inflammation was repressed in co-culture as compared to axenic, with reduced expression of executor and pyroptosis caspases; reduced expression of activators and increased expression of inhibitors of NFKB ; reduced expression of toll-like-receptors ( TLR s) and increased expression of TOLLIP (a negative regulator of TLRs). Consistent with the presence of actively fermenting bacteria that produce lactate and acetate but do not produce butyrate, PPARA expression was increased while PPARG expression was reduced. As in germ-free animal experiments, axenic human colonic mucosa is poised for inflammation. Co-culture with Bifidobacterium longum resolved the pro-inflammatory state while modulating barrier function (via Claudin genes) and cellular energetics (via PPARA and PPARG genes).

#2

This is exactly what this strain of probiotic might be capable of, increasing expression of raldh2 in the intestine.

Age-Dependent Decrease in the Induction of Regulatory T Cells Is Associated With Decreased Expression of RALDH2 in Mesenteric Lymph Node Dendritic Cells

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01555/full#:~:text=10.3389%2Ffimmu.2020.01555-,Age-Dependent%20Decrease%20in%20the%20Induction%20of%20Regulatory%20T%20Cells,Mesenteric%20Lymph%20Node%20Dendritic%20Cells&text=A%20decline%20in%20immune%20function%20with%20aging%20has%20been%20reported.&text=Finally%2C%20we%20found%20that%20RA%20treatment%20tended%20to%20increase%20Treg%20induction.

A decline in immune function with aging has been reported. Regulatory T cell (Treg) induction is known to decrease with age, and elucidating the underlying mechanism is important for preventing age-related diseases due to age-related chronic inflammation. In the intestine, dendritic cells (DCs) play an important role in inducing Tregs specific to oral antigens, and they efficiently induce Tregs via production of retinoic acid (RA), a vitamin A metabolite, catalyzed by the enzyme retinaldehyde dehydrogenase 2 (RALDH2).

A report by Bian et al. suggested that ALDH activity was reduced in conjunctiva cells of aged mice, which contributed to the inflammation that causes dry eye (31). Taken together with our results, it is suggested that the anti-inflammatory response is reduced in aged mice by a common process of RALDH reduction in mucosal immune systems. Although we focused on the intestinal immune system, considering that the Tregs induced in the intestine may circulate throughout the body, the decrease of Treg induction in the intestine may lead to systemic inflammation.