Ninety percent of our cells are made up of non-human organisms and 99% of those organisms reside within the human gastrointestinal tract known as our gut flora or microbiota. The composition of the microbiome is different from person to person and we each have our own individual and unique microbial footprint that determines and directs major functions within the human body. These intestinal organisms control metabolic rate, appetite, mood, immune system function and even direct how genes are expressed. They also have an influence over heart health, bone development and the integrity of our skin.
In the gastrointestinal tract the microbiome bacteria function to supply essential nutrients by breaking down complex carbohydrates, supporting the production of bile acids that assist in digesting fats and synthesizing vitamins K, B12, folate and biotin. The mucosal immune system is dependent on microbiome influences to maintain homeostasis and prevent autoimmunity.
The gut is often referred to as the “second brain” because of the direct connection between our microbiome and the function of the central nervous system. Our gut flora provides the communication between the central nervous system and the enteric nervous system by modulating the hormonal and neural pathways referred to as the gut-brain axis. Having an appropriate balance of gut flora contributes to psychological stability and positive mental health.
As an example of this relationship, serotonin is a brain neurotransmitter for which an entire class of drugs, e.g., selective serotonin reuptake inhibitors (SSRI’s), has been created to enhance mood, emotional stability and cognitive function. In the brain, serotonin has influences on appetite control, sleep, memory and learning, temperature regulation, social behavior and mood. Peripherally, serotonin is made in the gut and its production is dependent upon the presence of healthy gut flora.
A study comparing the serotonin levels in germ-free mice and mice with normal gut bacteria showed that 60% less serotonin was produced peripherally in the germ-free mice when compared to their healthy gut flora counterparts. Interestingly, when these germ-free mice were recolonized with normal gut microbes, the serotonin levels went up showing that a deficit in serotonin can be reversed.
The serotonin produced in the gut seems to be reliant upon the interaction of gut bacteria with the host and is likely produced by the bacteria itself. To further understand the interaction between the gut bacteria and the host, researchers began looking for key molecules that might mediate the formation of serotonin. They found several different metabolites from spore-forming bacteria that correlated with elevated levels of serotonin. This result would indicate that the balance of flora within the gut has a major influence over how much serotonin is produced peripherally. While adequate serotonin in the brain is associated with a stable mood and better cognitive function, high levels of serotonin in the brain leads to serotonin syndrome. Over-production of serotonin peripherally in the gut can contribute to IBS-D (diarrhea) while low serotonin production contributes too IBS-C (constipation). Finding the right balance of gut flora seems key to resolving the fluctuating symptoms of IBS.
As mentioned previously, serotonin regulates appetite and SSRI’s have been prescribed for weight loss with minimal success. However, what we really should be looking at is the relationship between our microbiome and metabolism. The typical western diet, coupled with decreased physical activity are major contributors to gut flora dysbiosis. A healthy balance of gut bacteria breaks down fiber into short chain fatty acids (SCFAs) which are associated with increased satiety, decreased food intake, lower levels of inflammation and improved insulin signaling in adipose tissue. Some studies have shown that a proportional increase in gram-negative bacteria in gut flora results in an increase in lipopolysaccharides (LPS). Increased LPS levels lead to a condition defined as “metabolic endotoxemia” which contributes to weight gain, fasting hyperglycemia and hyperinsulinemia.
Gram-negative bacteria that are common findings on a stool pathogen screen such as the comprehensive stool analysis from Mosaic Diagnostics Laboratory can detect: Yersinia, Pseudomonas, Proteus, Klebsiella, Helicobacter, Enterobacter, Campylobacter and E. coli. LPS is a protein fragment located in the outer membrane of gram-negative bacteria. When these bacteria die, they release LPS which can be absorbed into general circulation and promote chronic low-level inflammation. The absorption of LPS is promoted by a high fat diet, however, the studies do not differentiate between different types of fats.
In mouse studies, colonic flora was greatly altered to favor gram-negative bacteria when the mice were put on a high fat, low carb diet. Mice with normal receptors (CD14) for LPS showed increased cytokine activity in the liver within 2 weeks of a high fat diet leading to impaired metabolism and the development of hepatic steatosis. The studies performed on mice confirmed that LPS is a strong stimulator of the release of several cytokines that are key inducers of insulin resistance. It is important to note that plasma LPS levels are dependent on the combination of a high fat diet coupled with the presence of an abundance of gram-negative gut bacteria.
In one study (1), the endotoxin-producing bacterium, Enterobacter cloacae was isolated from a morbidly obese human’s gut and inserted into the guts of germ-free mice. The result was an induced obesity and insulin resistance in those mice and increased levels of serum LPS. The authors concluded that an increase of endotoxin-producing bacteria in gut microbiota, represents a cause, rather than a consequence, of the host’s metabolic balance deterioration. The results of the noted study imply that lowering metabolic endotoxemia could represent a potential treatment strategy for metabolic disease.
In considering strategies to address metabolic syndrome, the first step should be to evaluate gut flora and rule out infections that would undermine the delicate balance within the microbiota. Once infections are treated appropriately and confirmed to be resolved, we can go about restoring balance to the gut flora. One way of preventing the absorption of LPS from the gut is to ensure an adequate supply of prebiotics and fiber in the diet. This can often be achieved by consuming oligosaccharide-rich vegetables such as onions, leeks, garlic, asparagus, jicama and Jerusalem artichokes. Prebiotics in combination with Bifidobacter and Lactobacillus species reduce endotoxin absorption and improve mucosal barrier function. Including fermented foods such as cultured vegetables, natto and high-quality plain yogurt and kefir are also great ways to improve digestion and add prebiotics and probiotics to your diet in the form of food.
References
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448089/.Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239493/.Gut Microbiota and Metabolic Syndrome
3. https://www.caltech.edu/news/microbes-help-produce-serotonin-gut-46495. Microbes Help Produce Serotonin in Gut.
4. http://www.medscape.com/viewarticle/560887 Diabetes. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263193/. Management of Metabolic Syndrome Through Probiotic and Prebiotic Interventions
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