TDCA bile acid protects gut against lipopolysaccharide (LPS) endotoxin from bacteria

[cs3000]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904360/

"Dietary TDCA supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury.
Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation, and increasing villus length. Taurodeoxycholic acid supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection."


"68% vs. 28% survival.
The mice that lived beyond the initial 4 days all seemed to recover to their pre-injection activity. However, among the living mice, those that received the TDCA supplemented diet seemed to recover quicker from the insult compared to those animals that did not receive the TDCA. Similar results were reproduced on 3 separate survival trials in order to ensure that the results were accurate.

As expected, crypt apoptosis was significantly increased in those animals that received LPS when compared to NS by both H&E (104.7 ± 12.3 vs. 36.0 ± 5.5 per 100 crypts; Fig. 2A-B, G) and active caspase-3 staining (72.8 ± 12.5 vs. 4.0 ± 1.8 per 100 crypts; Fig. 2D-E, H). With the addition of TDCA to the liquid diet, crypt apoptosis in mice given LPS was significantly decreased when measured by both H&E (60.5 ± 2.7 per 100 crypts; Fig. 2C, G) and caspase-3 (18.7 ± 2.1 per 100 crypts; Fig. 2F, H).

Villus length was significantly decreased in mice that received LPS when compared to those that received NS (328.3 ± 10.7μm vs. 385.2 ± 20.7μm; Fig. 4A-B, D). When mice received TDCA supplementation, however, the LPS-induced loss of villus length was diminished (365.7 ± 11.1μm; Fig. 4C, D).

Although we estimated that each animal received 50mg/kg/day, this was not measured precisely; mice may have received more or less of the daily dose depending on how much food they consumed. Another possible limitation is that the mice were treated with the TDCA supplementation before the time of injury"


Dose used was ~250mg - 300mg TUDC human equivalent dose (but they said they didn't control well for it, that's their estimate).
& obviously that's a big amount of LPS to cause such drastic effects. so a much smaller dose would probably be beneficial for typical protection.

something to find out about this is if there's any significant cholesterol lowering effect from these low doses. and if there's unwanted conversion to Lithocholic acid from these conjugated bile acids which happens with UDCA

 

[cs3000]

Dose used was ~250mg - 300mg TUDC human equivalent dose (but they said they didn't control well for it, that's their estimate).
& obviously that's a big amount of LPS to cause such drastic effects. so a much smaller dose would probably be beneficial for typical protection.

something to find out about this is if there's any significant cholesterol lowering effect from these low doses. and if there's unwanted conversion to Lithocholic acid from these conjugated bile acids which happens with UDCA

Looks to lower cholesterol a bit but doesn't look hugely problematic in terms of lowering cholesterol at these doses 250mg - 500mg. If TUDCA is similar to TUDC, and UDCA

study with UDCA Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans
12 adults aged 24–36 years took 15 mg/kg/day ursodeoxycholic acid (UDCA) [in divided doses] or no bile acid supplement (control) for 20 days while being fed a controlled diet.

plasma total, HDL, and LDL cholesterol were unchanged with UDCA treatment.
After 14 days of diet alone, the plasma total cholesterol concentration was 152.8 ± 2.2 mg/dl, HDL cholesterol was 45.7 ± 1.1 mg/dl, LDL cholesterol was 93.8 ± 2.5 mg/dl, and plasma triglycerides were 73.7 ± 5.2 mg/dl. After 14 days of diet plus UDCA at a dose of 15 mg/kg/day, there was no change (all P = ns) in the plasma cholesterol (149.6 ± 2.2 mg/dl), HDL cholesterol (46.3 ± 1.1 mg/dl), plasma LDL cholesterol (89.75 ± 2.5 mg/dl), or plasma triglyceride (73.7 ± 5.2 mg/dl) concentrations.

Thus, despite marked enrichment in luminal bile with UDCA and decreased cholesterol solubilization, no differences in cholesterol absorption or metabolism are found when diet and genetic differences in absorption are carefully controlled.

^ you can see a mild drop in cholesterol levels. over 2 weeks this was about -5% LDL.

there's a meta analysis that put total cholesterol drop from taking UDCA in people without bilary blockage ~13mg/dl in total cholesterol, mainly from LDL at -6.66 mg/dL and triglycerides. in people with blockages that have jacked up cholesterol levels it might be more profound as that gets fixed, but you'd probably know about that with blood levels

https://lipidworld.biomedcentral.com/articles/10.1186/s12944-019-1041-4
so typically <10% reduction , and most the studies probably used 500mg - 1g+


also no lithocholic acid in bile was identified with either regimen

CDCA forms should be avoided in ppl with gallstones as it decreases HDL drastically in people with normal lipids & gallstones at 1g Different effects of chenodeoxycholic acid and ursodeoxycholic acid on serum lipoprotein concentrations in patients with radiolucent gallstones - PubMed but in people without gallstones at 600mg it actually increased Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial


Considering taking UDCA raises TUDCA levels i think they'd have the same mild impact on cholesterol in ppl without bile blockages. TUDCA isn't TDCA used in the study but that's the supplement accessible, probably works similar:
Tauroursodeoxycholic acid inhibits experimental colitis by preventing early intestinal epithelial cell death - Laboratory Investigation Whereas vehicle-treated mice showed a cumulative mortality of 40%, all TUDCA-treated mice survived the DSS experiment during a 14-day follow-up period. In line with a barrier protective effect, TUDCA decreased bacterial translocation to the spleen and stimulated mucin production. Similarly, TUDCA inhibited lipopolysaccharide-induced intestinal permeability and associated enterocyte apoptosis

https://www.gastrojournal.org/artic...pdf?referrer=https://www.semanticscholar.org/
^ Another one on people with higher cholesterol intakes & different measurement method

This one uses both UDCA and TUDCA - shows bile acid synthesis is not reduced when taking bile acids
"Maintenance of these pool sizes further suggested that fed UDCA and TUDCA were not effectively suppressing endogenous bile acid synthesis."

So there's no reliance on these unless your baseline is already lacking. you just go back to the same level of bile acids you were at before starting the supplement

It showed a moderate lowering of cholesterol absorption over a month. 15mg/kg and 20mg/kg
Calculated % cholesterol absorption: controls: 57% UDCA: 47% TUDCA: 42%


Micellar solubilisation of cholesterol is essential for absorption in humans in children lacking bile acids supplementing them actually increases cholesterol absorption , and cholesterol synthesis lowers as a feedback mechanism to balance

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So basically from doses <1g you could reasonably expect -5%-10% drop in cholesterol.
lower doses 250mg-500mg probably less. another rat study showed 500mg TUDCA human equivalent was the dose that lowered gut inflammation.