I have discussed the evidence linking the mix of bacteria in your gut (gut flora) to health and disease in Part I. The Bacteria in your Gut are essential to your health Part I | Practical Evolutionary Health
Today I will discuss the evidence related specifically to obesity and metabolic syndrome (the constellation of obesity, insulin resistance, high blood pressure, and abnormal blood lipids). My discussion will follow closely the evidence and theory presented in research and review papers authored by Dr. Cani and colleagues. The first one is titled:
“Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.”
You can find the full text of this article here .
I have had the pleasure of corresponding with Dr. Cani by e-mail regarding her many publications investigating the relationship between gut flora, obesity, and metabolic syndrome.
“Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis).”
Explanation: The gut microbiota are the bacteria, viruses and other “bugs” that reside in our intestines. Insulin resistance can occur in various parts of the body, wherever insulin has an effect including fat cells, liver, muscle, brain. When higher amounts of insulin are required to achieve an effect this is called insulin resistance. In Type 2 diabetes, the pancreas is still able to make insulin but insulin is less effective in controlling blood sugar. In Type I diabetes the pancreas no longer produces insulin. Hepatic Steatosis means fatty liver disease. The liver accumulates fat and this can lead to cirrhosis, liver failure and death. Alcohol consumption can cause this but when alcohol is not involved this is called Non-Alcoholic-Fatty-Liver Disease (NAFLD). Our nation presently has an epidemic of not just obesity but also NAFLD. Evidence points to excess carbohydrate consumption and excess consumption of vegetable oils (linoleic acid) as contributing factors in NAFLD. Carbohydrate restriction and consumption of saturated fat, particularly medium chain fats (as found in coconut) can protect against NAFLD. But the gut flora also play a role. The mechanisms involved are many.
“Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance.”
Endotoxemia occurs when a toxin from certain kinds of bacteria circulates in the blood. This endotoxin enters our blood through our intestines under conditions in which the protective barrier of the intestines is compromised. The compromise of the intestinal barrier is variously referred to as ” leaky gut” or “increased intestinal permeability”. Wheat gluten-gliadin causes increased intestinal permeability (especially in celiac disease) as can other plant lectins. In this discussion, the gut bacteria also contribute in the setting of “dysbiosis” (the beneficial effects of helpful bacteria are overwhelmed by the harm-causing bacteria when a healthy balance is not present)
Lipopolysaccharide (LPS) comes from the outer wall membrane of certain bacteria. Blood plasma is the liquid part of blood in which the blood cells circulate. So an “increase in plasma lipopolysaccharide” simply means that there is more LPS circulating in the blood. That is a bad thing. Depending on how much is circulating this alone can cause organ failure and death and is a major part of the physiologic changes involved in septic shock. But lower levels of LPS circulating in the blood can cause chronic low grade inflammation and insulin resistance. Obesity is associated with chronic inflammation and increased LPS circulating in the blood and being distributed to various organs where it wreaks havoc.
“Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterizing these metabolic disorders via mechanisms associated with gut barrier dysfunctions.”
“We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia.”
That is a mouth-full. Over thirty different kinds of hormone producing cells have been found in the human intestine. These cells are called enteroendocrine cells. The hormones produced by these cells have many effects. You can find a great review of these cells and their effects here .
In Dr. Cani’s review article she describes how some of these hormones produced in the gut can increase intestinal permeability and allow more of the toxic, inflammation producing LPS to enter the bloodstream. But these hormonal effects are just part of the picture. Another part relates to endocannabinoids.
The Endocannabinoid system in humans is complex and relates to hunger, satiety, energy metabolism, and yes gut permeability. Endocannabinoid refers to our internal (endo) production of cannabis like substances. Pot smoking people get the munchies because of the appetite stimulating effects of marijuana. But endocannabinoids have many other physiologic effects including the modulation of pain, mood, immune function and memory.
Dr. Cani describes in great detail the evidence supporting the roles that the gut flora play in influencing intestinal permeability mediated through the effects of various hormones and endocannabinoids. In animal and human studies changing the gut flora produces changes in these hormones and endocannabinoids which in turn can increase or decrease intestinal permeability and increase or decrease circulating LPS.
It turns out that specific Prebiotics can produce growth of beneficial gut bacteria and through the series of steps outlined above, reduce inflammation in the body, improve blood sugar, improve insulin sensitivity, and decrease fat,
Oh, and similar to the endocannabinoid system, there is an “apelinergic system” in our bodies that also plays a role. If you want to read more about these systems you should read the original article and the other links below to related articles.
I have discussed in the past that fecal transplants have been used to treat the specific dysbiosis that occurs with C Difficile colitis. But fecal transplants have many potential beneficial uses.
The Fatlose 2 trial is presently studying the effects of fecal transplants on insulin resistance and related problems in human volunteers. I will let you know when the results are published, Studies conducted in rodents have demonstrated significant weight loss and improved insulin sensitivity when obese rodents receive fecal transplants from lean rodents.
In summary: dysbiosis represents an unhealthy mix of bacteria in the gut
- dysbiosis causes increased intestinal permeability (leaky gut)
- increased intestinal permeability leads to increased circulating LPS, which is bad
- elevated levels of circulating LPS create a chronic state of inflammation which contributes to obesity and metabolic syndrome
- the mechanisms that link dysbiosis to intestinal permeability include hormonal disruption (enteroendocrine cells) and the endocannabinoid system. Other mechanisms are also likely in play.
- prebiotics and probiotics can mitigate dysbiosis, reduce intestinal permeability, reduce inflammation, and offer potential therapy for obesity and metabolic syndrome
- fecal transplantation offers a potential for treatment for obesity and metabolic syndrome, research is underway
Our ancestors lived and evolved for a few million years prior to the relatively brief ten thousand years of agriculture and one hundred years of industrialization. The overuse of antibiotics in medicine and animal husbandry have contributed to dysbiosis. Other factors include stress, disruption of circadian rhythm, sleep deprivation. Cesarean delivery and avoidance of breast feeding conspire to dysbiosis. Processed foods feed unfriendly bacteria in our guts at the expense of beneficial bugs. Agricultural foods have introduced dietary lectins which also increase intestinal permeability and thereby contribute to chronic inflammation. The further we stray from our evolutionary niche, the more problems we experience.
This discussion just touches the surface of gut flora, dysbiosis, health and disease. We have yet to explore the gut-brain axis. Our gut and microflora communicate with and effect the function of our brain and other organs as well.
We will continue to explore health and disease from an evolutionary perspective.
Below are links to articles related to our discussion.
Peace, health and happiness.
Gut microbiota controls adipose tissue expans… [Benef Microbes. 2014] – PubMed – NCBI
Glucose metabolism: Focus on gut microbiota, … [Diabetes Metab. 2014] – PubMed – NCBI
Probiotics, prebiotics, and the host microb… [Ann N Y Acad Sci. 2013] – PubMed – NCBI
Crosstalk between the gut microbiota a… [Clin Microbiol Infect. 2012] – PubMed – NCBI
Gut microbiota and its possible relationship … [Mayo Clin Proc. 2008] – PubMed – NCBI
Enteroendocrine Cells: Neglected Players in Gastrointestinal Disorders?