In this post, I want to talk about the various functions beneficial gut flora, and their metabolites play in our health. One thing needs to be mentioned at the start. Many of the following studies were done on rats, mice and other animals. What’s true of animal studies is not always relevant to people until confirmed in human trials. That said, there is enough evidence in humans to suggest that what is true for these animal is true for us although the particular bacterial strains and mechanism of action may prove to be different.
Much, although not all, of what follows is a synopsis of a great overview paper from McGill University entitled: Gut Microbiota: next frontier in understanding human health and development of biotherapeutics. (1) For those of you interested in reading the original paper, you may access it for free here. The authors of this paper divide the functions of gut flora into three broad categories: metabolic, protective and structural/cellular. I’ll add a fourth function called the gut-brain-flora axis.
Beneficial gut flora are responsible for the production of B vitamins and vitamin K2. Although you also get these vitamins in a nutrient-rich diet, beneficial gut flora makes sure these vital vitamins are never in short supply.
B vitamins help reduce inflammatory homocysteine levels and are involved in cell metabolism, blood pressure regulation and immune system function. Vitamin K2 is necessary for proper blood clotting and strong bones and teeth.
Commensal gut flora are involved in maintaining proper levels of bile acid. In a study with mice treated with an antibiotic, negative alterations were noted in the metabolism of bile acids. Fewer beneficial bacteria in these mice led to higher bile acid production in their livers as well as increased reabsorption from their intestines while simultaneously reducing excretion of bile in feces. (2)
Large amounts of bile can be toxic to cells within the liver and intestines so any disruption in inhibitory mechanisms may predispose to gallstone disease, liver injury and inflammation predisposing to colon cancer.
The malabsorption of fat due to improper bile acid metabolism has also been implicated in irritable bowel disease due to small intestinal bacterial overgrowth. (3) Proper bile metabolism is also essential for digestion of fat in the diet and absorption of fat-soluble vitamins and minerals and plays a role in cholesterol and glucose production in the liver.
Beneficial bacteria produce, via fermentation, a number of end products or metabolites that are necessary for many physiological functions. In the colon bifidobacteria ferment what are classified as prebiotics or non-digestible carbohydrates into short-chain fatty acids. The three major fatty acids produced are acetate, butyrate and propionate.
Acetate quickly departs the colon to be used by the liver, muscles and other tissues throughout the body. In pigs, acetate has been found to stimulate sodium uptake. If this holds true for humans, acetate may help prevent recurrent diarrhea. (4)
Propionate is largely used to fuel liver function. It’s theorized that propionate may also reduce hunger in humans by increasing satiety signals to the brain. (5)
Butyrate is a major source of energy for the cells lining the colon providing up to 60-70% of the energy requirements for these cells. Simultaneously, it can supply the body with between 7-10% of its energy needs. (6) Butyrate has been shown to prevent carcinogenic activity in rats by inhibiting mammary tumor progression. (7) Finally, it has been proposed that the inability to use butyrate properly could be a predisposing cause of ulcerative colitis. (8)
Bifidobacteria has also been found to produce conjugated linoleic acid (CLA). (9) B. breve was the particular strain most likely to produce this important substance.
CLA is found naturally in the milk and tissue fat of ruminant animals and in the highest concentrations in grass-fed animals. CLA was demonstrated to have a number of positive physiological actions such as inhibiting weight gain, and having anti-diabetic, anti-carcinogenic and anti-atherosclerotic properties. (10)
In the pre-diabetic Zucker fatty rat, CLA normalized glucose levels. (11) CLA has also been shown to regulate the leptin hormone in rats and mice. (12) Leptin is a hormone produced in fat tissue that regulates long-term weight homeostasis. Finally, CLA positively influences calcium and bone metabolism. (13 – 15)
Either supplementing with bifidobacteria or encouraging its growth has also been shown to increase HDL levels in a small group of women, reduce lactose intolerance , have a modest effect in preventing infectious diarrhea, reduce triglyceride levels, improve glucose control and reduce inflammation and intestinal permeability. (16 – 23)
Like any ecosystem, certain species will thrive while others will not depending on the environment they live in. In a healthy gut, beneficial bacteria out compete pathogenic bacteria and yeast for attachment sites to the intestinal wall. They produce lactic acid which makes the mucosa an inhospitable environment for pathogens. They also out compete harmful organisms for nutrients from the food you eat.
Beneficial gut flora are vital for proper immune function along the length of the intestinal tract. Your largest exposure to the outside world is not your skin, it’s your digestive tract. Were you able to unfurl just your small intestine, it would cover a standard-size tennis court!
Even though your digestive tract is located within you, as far as your body is concerned, its contents are actually an external environment that must be protected against while simultaneously allowing the entry and digestion of the nutrients you need to thrive.
For this reason the majority of your immune defense cells are located here. Collectively referred to as the gut-associated lymphoid system or GALT, it’s comprised of many structures like Peyer’s patches, T lymphocytes, B lymphocytes and antigen presenting cells. This immune complex is on a continuous lookout for potentially harmful proteins, yeasts, bacteria and viruses that if allowed to breach the gut wall could compromise health via inflammatory immune responses.
In childhood, gut flora programs both the innate and adaptive arms of the immune system. (24) (25) The innate immune system is the first line of defense against novel pathogenic threats. The adaptive immune system is composed of those immune components that remember and respond to previous antigens.
Studies in germ-free mice have demonstrated underdeveloped immune structures within their intestinal tract. (26) (27)
Furthermore, evidence suggests a role for gut flora in the development of immune B and T cells. (28 – 31) Short-chain fatty acids produced by commensal bacteria in the colon have also exhibited immune regulatory effects. (32) (33)
Gut flora produce antibiotics against bacterial infections. For example, Latobacillus salivarius produced an anti-microbial substance in mice that protected the mice from foodborne Listeria monocytogenes infection. (34)
Probiotics have been shown to suppress proinflammatory signaling pathways in both epithelial and immune cells. As inflammation is the ultimate cause of all disease, this is a very important function. The pro-inflammatory pathways blocked include signaling molecules or cytokines like tumor necrosis factor (TNF) and interleukin 8. (35 – 38)
Finally, gut flora envelope and safely excrete foreign inorganic substances (xenobiotics) ingested with our food like lead, aluminum and mercury. This probably explains why some people are more susceptible to heavy-metal exposure than others. (39)
Structural and Cellular Function
Commensal gut flora is vital for maintaining the integrity of the intestinal wall and preventing increased intestinal permeability or “leaky gut.”
The production of butyrate by commensal gut flora reinforces the barrier in the colon. (40) Butyrate also regulates cell growth along the intestinal wall and inhibits cancerous cell growth. (41)
Other bacterial communities in the small intestine strengthen what are known as tight junctions. These gaps between the cells lining the small intestine are normally sealed to prevent intestinal contents from passing through to systemic circulation.
Germ-free animal studies show that beneficial bacteria regulate the cell cycle of the enterocytes that form the brush border of the small intestine. Helping to control not only how quickly these cells migrate from the base to the top of the finger-like projections or villi of the small intestine , but also the length of the villi itself. (42) (43) In other words, a healthy brush border, essential for the proper digestion of your food, production of vitamins and satiety hormones, is impossible without the cell regulating effects of commensal gut flora.
It has been long recognized that the brain can regulate gut activity. Anyone who has experienced “butterflies” in their stomach when engaging in a perceived or actually dangerous activity knows what I’m talking about. Many performers and public speakers get physically ill before going on stage.
Stress has very negative effects on intestinal barrier function increasing intestinal permeability in both the small and large intestine and promoting the growth of pathogens like E. coli. (44) (45)
What is less well-known is that communication between brain and gut is not one way, but bi-directional. The gut-brain-flora axis includes the central nervous system, the neuroendocrine or hormonal system, the neuroimmune system, both sympathetic and parasympathetic arms of the nervous system, the nerves in the GI tract or enteric nervous system and last, but by no means least, the gut microbiome.
The vagus nerve which connects your gut with your brain is the main line of communication between both. And its connection to the hypothalamus-pituitary-adrenal (HPA) axis means that all the physiological and psychological processes attributed to the HPA axis not only influence the gut and the gut flora but conversely, the gut and gut flora influences the HPA axis.
The use of germ-free mouse models has revealed a number of intriguing findings on how alterations in microbiota influences behavior and indicators of stress, anxiety and depression.
Elevated stress responses have been noted in germ-free mice with normalization after colonization with Bifidobacterium infantis. (46) In another study, treating mice for 28 days with Lactobacillus rhamnosus resulted in animals with lower stress hormones and reduced levels of depressive and anxious behaviors. (47)
Another study found that certain Lactobacillus strains could mimic the effects of morphine in reducing the perception of pain. (48)
Yet another study in rats found that Bifidobacterium infantis caused an increase in plasma tryptophan levels which is a precursor to serotonin. (49) Serotonin is a very important neurotransmitter that regulates mood, appetite, sleep, memory and learning.
While this is completely anecdotal, once I resolved my gut dysbiosis my insomnia went away. I never knew what sleep could be until relatively recently. Levels of stress and anxiety also came down. Where before I would “what if” myself into a frenzy over an impending trip, social or work function, I no longer feel that level of stress in those situations. I also feel more energetic and optimistic which was essential to starting and maintaining a business.
In the next post I’ll detail what can go wrong with your health when commensal bacterial populations are disturbed……
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