Bile Salt Biotransformations By Human Intestinal Bacteria

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
Bile salt biotransformations by human intestinal bacteria. - PubMed - NCBI

"Bacterial density in the human colon is among the highest found in nature, approaching 10^12 bacteria/g wet weight of feces (2, 3). In contrast, the host suppresses significant bacterial colonization of the small intestine by a variety of mechanisms, including rapid transit times, antimicrobial peptides, proteolytic enzymes, and bile (4). Failure of these mechanisms leads to bacterial overgrowth of the small intestine, resulting in malabsorption as bacteria compete with the host for nutrients. Under normal conditions, bacterial fermentation in the colon represents an important salvage mechanism."

"Colonic bacteria also contribute to the salvage of bile salts that escape active transport in the distal ileum."
"Deconjugation and 7a/b-dehydroxylation of bile salts increases their hydrophobicity and their Pka, thereby permitting their recovery via passive absorption across the colonic epithelium. However, the increased hydrophobicity of the transformed bile salts also is associated with increased toxic and metabolic effects. High concentrations of secondary bile acids in feces, blood, and bile have been linked to the pathogenesis of cholesterol gallstone disease and colon cancer (5)."

"Bile salts are highly effective detergents that promote solubilization, digestion, and absorption of dietary lipids and lipid-soluble vitamins throughout the small intestine. High concentrations of bile salts are maintained in the duodenum, jejunum, and proximal ileum, where fat digestion and absorption take place. Bile salts are then absorbed through high-affinity active transport in the distal ileum (6). Upon entering the bloodstream, bile salts are complexed to plasma proteins and returned to the liver. Upon reaching the liver, they are cleared efficiently from the circulation by active transporters on the sinusoidal membrane of hepatocytes and rapidly secreted into bile."
"During the enterohepatic circulation, bile salts encounter populations of facultative and anaerobic bacteria of relatively low numbers and diversity in the small bowel. Bile salt metabolism by small bowel microbes consists mainly of deconjugation and hydroxy group oxidation. Ileal bile salt transport is highly efficient (~95%), but approximately 400–800 mg of bile salts escapes the enterohepatic circulation daily and becomes substrate for significant microbial biotransforming reactions in the large bowel (6)."

"The bile acid conjugates glycine and taurine serve as substrates in microbial metabolism. Unlike glycine, taurine contains a sulfonic acid moiety that is reduced and dissimilated to hydrogen sulfide after deconjugation (38, 39). Hydrogen sulfide is highly toxic and has been shown to increase colonocyte turnover (40). Activation and upregulation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway has been suggested as a possible mechanism for sulfide-induced colonocyte proliferation (41). Hydrogen sulfide also inhibits butyrate metabolism in colonocytes, a key nutrient and regulator of cell turnover in the gut (40). Levitt et al. (42) demonstrated that colonocytes have evolved a highly efficient mechanism to detoxify volatile reduced sulfides through oxidation to thiosulfate. Defects in this detoxification system are suggested to play a role in the pathogenesis of ulcerative colitis, a known risk factor for colon cancer (42, 43)."

"SECONDARY BILE ACIDS AND DISEASE
In humans, DCA accumulates in the bile acid pool to high levels in some individuals. An increase in DCA in the bile acid pool is associated with a decrease in CDCA (Fig. 11). Unlike rodents, the human liver cannot 7ahydroxylate DCA, forming CA. Hence, under normal physiological conditions, there is no metabolic pathway for removing DCA from the bile acid pool in humans. The amount of DCA in the bile acid pool is a function of at least three variables: 1) the rate of formation and absorption of DCA through the colon (input) (132); 2) colonic transit time (133); and 3) colonic pH (134)."

"High levels of DCA in blood, bile, and feces have been correlated with an increased risk of cholesterol gallstone disease and colon cancer, two major diseases of Western society (5, 135). High levels of CA 7a-dehydroxylating fecal bacteria have been correlated with increased amounts of DCA in bile of a subset of cholesterol gallstone patients (132). Treatment of these cholesterol gallstone patients (high DCA group) with antibiotics significantly decreased the levels of fecal CA 7a-dehydroxylating bacteria, DCA in bile, and the cholesterol saturation index in bile (132). Early studies by Low-Beer and Nutter (135) reported that treating control individuals with metronidazole, an antibiotic effective against anaerobic bacteria, significantly decreased the cholesterol saturation index of bile. Moreover, excess DCA in bile has been reported to decrease the nucleation time for cholesterol crystallization (136, 137). In total, these results suggest a possible link between intestinal bacteria, DCA, and the risk of cholesterol gallstone disease in some patients."

"Higher levels of DCA are found in the blood of colon cancer patients compared with control patients (98, 143). Moreover, DCA is a logical candidate for promoting colon carcinogenesis for the following reasons: 1) it is found in fecal water in high concentrations (>100 mM) (138); 2) it can cross biological membranes via passive diffusion; and 3) it can activate mammalian cell signaling pathways that are known to be involved in promoting carcinogenesis."
"Secondary bile acids have been shown to cause apoptosis in colonic epithelial cells, and high concentrations of DCA and LCA in stool may promote carcinogenesis by exerting selective pressure for the emergence of epithelial cell mutants that are resistant to apoptosis (e.g., via loss of p53) (138). LCA has been found to be an excellent activator of the vitamin D receptor (149, 150). Activation of this receptor in intestinal epithelial cells activates genes that metabolize LCA (150). This may be a protective mechanism that evolved to limit LCA toxicity to intestinal epithelial cells."
 
Last edited:
Joined
Feb 1, 2016
Messages
384
Location
NY
Awesome post!!!

Probably another reason to keep fat low: less bile secretion=less bile that feeds putrefactive bacteria.
 

Nighteyes

Member
Joined
Sep 5, 2015
Messages
411
Location
Europe
Its late where I live and I have a hard time completely understanding taurine and glycines's actions here. Taurine is turned into Hydrogen sulfide, which is highly toxic? I thought taurine improved bile secretion and was a good thing? I am confused and any simple explanations would be welcome.'


"The bile acid conjugates glycine and taurine serve as substrates in microbial metabolism. Unlike glycine, taurine contains a sulfonic acid moiety that is reduced and dissimilated to hydrogen sulfide after deconjugation"

Dictionary says dissimilation is to make "unsimilar to".. what on earth does this mean in relation to taurine and hydrogen sulfide.. ?
 
Last edited:
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
Its late where I live and I have a hard time completely understanding taurine and glycines's actions here. Taurine is turned into Hydrogen sulfide, which is highly toxic? I thought taurine improved bile secretion and was a good thing? I am confused and any simple explanations would be welcome.'


"The bile acid conjugates glycine and taurine serve as substrates in microbial metabolism. Unlike glycine, taurine contains a sulfonic acid moiety that is reduced and dissimilated to hydrogen sulfide after deconjugation"

Dictionary says dissimilation is to make "unsimilar to".. what on earth does this mean in relation to taurine and hydrogen sulfide.. ?
You skipped the following part:
"Levitt et al. (42) demonstrated that colonocytes have evolved a highly efficient mechanism to detoxify volatile reduced sulfides through oxidation to thiosulfate. Defects in this detoxification system are suggested to play a role in the pathogenesis of ulcerative colitis, a known risk factor for colon cancer (42, 43)."
 

Nighteyes

Member
Joined
Sep 5, 2015
Messages
411
Location
Europe
Yes - i guess i have a hard time grasping The whole bile acid/bile salt cycle and Taurine and glycines interactions.. English is not my first language.

Is this one of The benefits of carrot fiber - that is carries excess unwanted bile through The colon?
 
Last edited:
Joined
Feb 1, 2016
Messages
384
Location
NY
How low do you keep fat?
I try to keep it under 50 grams a day, but its hard for me to get enough calories without either eating more fat or eating starch. Eating a bunch of sugar and coconut oil can get lots of calories, but then I will quickly run out of nutrients and become hypometabolic.
 
Joined
Jan 24, 2014
Messages
1,750
Sounds to me like all the more reason to eat the carrot salad daily or at least keep a higher level of fiber in your diet to bind the estrogen soaked bacterial laden bile and carry it out the back door. PRONTO!

I've read several studies that showed the presence of LIVE BACTERIA in gallstones that were cut open and cultured. The link below shows the bacteria responsible for typhoid actively forms a biofilm on gallstones and people can be carriers and spread typhoid fever while being asymptomatic themselves. Biofilms on gallstones...who knew?

Typhoid Fever Bacteria Collect On Gallstones To Perpetuate Disease
 

EIRE24

Member
Joined
Apr 9, 2015
Messages
1,792
I try to keep it under 50 grams a day, but its hard for me to get enough calories without either eating more fat or eating starch. Eating a bunch of sugar and coconut oil can get lots of calories, but then I will quickly run out of nutrients and become hypometabolic.

How do you mean by hypometabolic? I'm guessing it's not really a very low fat diet then? I tried to switch to a low fat diet with mainly dried fruit, fresh fruit, dairy and gelatin but my skin broke out in acne, it also became dry and irritated looking. I'm wondering if maybe a low fat diet could cause dry skin which in turn caused the acne?
 
Joined
Feb 1, 2016
Messages
384
Location
NY
Hypometabolic denotes a lower metabolic rate. Maybe the dry skin caused the acne, who knows. The lower fat you go, the more sugar you burn, and burning sugar is a more involved process for the body. It requires more vitamins/minerals to be sustained. If you can't sustain it, your body will catabolize and you and your skin will suffer.

The balance of nutrients in fruits is favorable for sugar burning, however a higher fat intake can make sense given the general depletion of the soil.

Go by craving
 

EIRE24

Member
Joined
Apr 9, 2015
Messages
1,792
Hypometabolic denotes a lower metabolic rate. Maybe the dry skin caused the acne, who knows. The lower fat you go, the more sugar you burn, and burning sugar is a more involved process for the body. It requires more vitamins/minerals to be sustained. If you can't sustain it, your body will catabolize and you and your skin will suffer.

The balance of nutrients in fruits is favorable for sugar burning, however a higher fat intake can make sense given the general depletion of the soil.

Go by craving


That makes a lot of sense. I used to have a low fat diet but it was a lot higher in protein through stuff like protein powders and the like. I also did eat a fair amount of pufa from crappy food sources. I'm guessing this never allowed me to burn sugar properly thus my skin was being saved?
 
J

James IV

Guest
Interesting. Just to add to the real world data. When i went very low fat and high sugar, I started to have many signs of bacterial overgrowth. I had infected skin in my armpits, and on the sides of my head. I had large cracks in my tongue and a white coating. I also experienced constipation and new body hair growth, which I believe is a sign of bacteria proliferation in the skin.
When I dropped my sugars down and upped my fats again all of these symptoms began clearing up and I started releasing fecal matter that looked/smelled like it had been built up in my system for a while.
There may be some advantages to lowish fat, but I think bile is important to keep the system "clean" and going too low in fat for too long may be detrimental.
 

Similar threads

Back
Top Bottom