Ok, it’s time for me to tackle a topic that is totally new to me. Today’s subject: bile acids. It may not sound exciting but it turns out, bile acids have a huge part to play in your health, and that effect is based upon the contents of your microbiome.
Several months ago, I first stumbled across the topic when I came upon a 2014 article out of the University of California, Davis, relating bile acid dysregulation to gut dysbiosis and gastrointestinal (GI) cancer.[i] Before I describe this, and then some new research, let’s start with a definition. Bile acids (BA) are made by your liver to break down fat that you eat. They are derived from cholesterol. Primary bile acids, secreted by the liver into your GI tract, are then converted into secondary bile acids by enzymes secreted by your gut bacteria.
According to that 2014 article, our modern diet, which is high in (unhealthy) fat and sugar (along with other factors, including lack of physical exercise, etc.) has led to the current epidemic of obesity and diabetes, both of which are linked to an increased risk for cancer. Both diabetes and obesity have also been linked to dysregulation of bile acids and also, dysbiosis of the microbiome. Subsequent elevated levels of secondary bile acids, along with a pro-inflammatory shift in the bacterial microbiome, have been linked to cancer: “…recent findings have implicated a detrimental interplay between BA dysregulation and intestinal dysbiosis that promotes carcinogenesis along the gut-liver axis.”
The exact mechanisms are, of course, not as yet understood…which brings me to two new pieces of research out of Harvard.[ii] Just as too much is not good, neither is too little. To boot, BA have a direct major effect upon the immune system.
It turns out that bile acids “…promote the differentiation and activity of several types of T cells involved in regulating inflammation and linked inflammatory conditions.” And as the bacteria of the gut are critical in converting bile acids into secondary bile acids, and immune-signaling molecules, they are also critical in this immunological process.
The first study showed, in an animal model, that bile acids, once converted into these immune-regulatory molecules by gut bacteria, activate two kinds of immune cells: Treg (T regulatory cells, which are the off-switch to the inflammatory system) and T helper (effector) cells, Th17, which are proinflammatory. Of course, to remain healthy, you need an inflammatory response to fight pathogens, and you equally need a regulatory system to turn that inflammation off when it’s no longer needed. There is a crucial balance between the two. These researchers found that two particular bile acid molecules affected Treg and Th17, and these two molecules are indeed found in human stool, which suggests that this research also applies to us. Says the lead researcher on this study, “Our findings identify an important regulatory mechanism in gut immunity, showing that microbes in our intestines can modify bile acids and turn them into regulators of inflammation.”
If these findings are confirmed in humans, these natural molecules can be used to modulate inflammation in diseases affecting the gut, like inflammatory bowel diseases (IBD).
The second Harvard study showed that gut microbes and diet “…work in concert to modify bile acids, which in turn affect the levels of colonic Tregs in mice.” Low levels of Treg cells, from low levels of bile acids, make the mice prone to developing inflammatory conditions, like IBD. This study is a bit more complicated, and involved populating mice with gut bacteria in which genes which are responsible for BA conversion (into these immune-signaling molecules) are silenced. They then put these bacteria, or normal bacteria, back into germ-free mice. Those animals who were given the modified bacteria had markedly lower levels of Treg cells (and therefore, higher inflammation). In other words, gut microbes which convert BA are critical for gut health.
They then tested the effects of diet. Animals fed minimal diets had low levels of BA and thus, low levels of Treg, which of course makes senses. Fat in the diet is what stimulates the body to produce BA after all. However, animals with germ-free guts who received rich diets also had low levels of Treg, proving that gut microbes are crucial in producing those immune-signaling molecules from BA.
In a second part of their experiment, the scientists broke up the mice into 3 groups. The first was fed a minimal diet. The second was fed a nutrient-free diet and the third group was fed minimal food, but was also supplemented with bile acid signaling molecules. All three groups were then given a substance that induces colitis. Not surprisingly, only the animals fed a minimal diet who were not supplemented with the BA molecules actually went on to develop the disease.
Back then to that first 2014 article: it concludes with a section which suggests that there are potential treatments for BA dysregulation, which include probiotics and prebiotics (to improve the quality of the microbiome), as well as dietary changes. For example, vitamin B6 has been shown to improve colon health. Other natural substances include burdock root (from a plant in the daisy family) powder and genistein (an isoflavone derived from plants like soy), which have shown, “…moderate efficacy in normalizing BA homeostasis and the gut microbiome in animal models.”
If you think about it, diet is crucial in more ways than one. That is, a healthy diet, rich in nutrients, is crucial for the stimulation of BA, as shown by the above studies. Diet is crucial for maintaining a healthy weight and thus, avoiding the inflammation discussed in the 2014 article. And diet also modulates the health of the microbiome, thereby indirectly affecting inflammation by affecting the bacteria responsible for converting BA into the immune-signaling molecules necessary to maintain health.
So your take home message is, yet again, eat a health diet!
[i] Tsuei, J, Chau, T, Mills, D, Wan, YJY. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer. Experimental Biology and Medicine. 2014; 239(11): 1489–1504. doi:10.1177/1535370214538743.
Category: Bacterial Microbiome, Bile Acids, cancer, Crohn's, Crohn's Disease, Diabetes, Diet, Human Biome, inflammation, Inflammatory Bowel Disease, Metabolic Syndrome, microbiome, obesity, Ulcerative ColitisTags: bacterialmicrobiome, bileacids, cancer, Crohn's, Diabetes, Diet, gutbacteria, health, inflammatoryboweldisease, metabolicsyndrome, microbes, ulcerativecolitis