How Microbiome-Driven Inflammation Promotes Weight Gain and Diabetes

Think that problems with your gut health only impact digestive symptoms? Think again!

In this talk, we discuss the research on how imbalances of the gut microbiome can promote risk of obesity, type 2 diabetes, fatty liver, and metabolic syndrome. We’ll also share some practical tips for how to improve this problem if you struggle with your weight and metabolism.

During our podcast episode, we unpack:

  • The function of our gut microbiome
  • The impacts of having a diverse microbiome
  • The impacts of not having a diverse microbiome
  • The impact of dysbiosis on inflammation
  • Indications of systemic inflammation
  • What the research indicates
  • And finally, the tools you can use to repair your gut lining

Take a listen! Your gut will thank you.

Let’s dive even deeper into the gut and its role on our metabolism!

What is metabolic endotoxemia?

The gastrointestinal (GI) tract is a host to billions of microorganisms that break down our food, manufacture vitamins, and control our immune system. Essentially, it’s thought of as an extra organ in your body and they play a huge role in our health.

Healthy individuals are characterized by having a diverse gut microbiome with an intact intestinal lining.  Humans with metabolic dysregulation (such as obesity, type two diabetes, metabolic syndrome, non-alcoholic fatty liver disease, etc.) show a less diverse microbiome, overgrown “bad” bacteria– dysbiosis– with more detrimental pathogens compromised intestinal lining, and systemic inflammation.

Essentially, metabolic endotoxemia is dysbiosis that affects the gut lining, creating pro-inflammatory immune responses that put your body in a state of chronic inflammation.

Research has shown that chronic systemic inflammation can be seen as the starting point for developing metabolic disorders: obesity, type 2 diabetes, non-alcoholic fatty liver disease.

How does it work?

The food that you eat will break down to its simplest form and also feed your gut bacteria.

A diet that consists of high fiber and a high intake of plants will feed good bacteria that then produce short chain fatty acids that get metabolized in the liver that ultimately improve glycemic control.

A high-fat diet (the ever-popular ketogenic diet included) will feed the more detrimental bacteria, and their endotoxins (waste) will produce lipopolysaccharides (LPS) which increase the permeability across the intestinal lining. Now the bacterial waste products are no longer in your GI tract, but they are circulating in your blood, causing the body to release a mass production of pro-inflammatory cytokine– not good!

What happens when the gut lining is compromised?

Leakage of bacteria and their toxins are released into the bloodstream. Your body knows these toxins are not supposed to be in the gut, so it releases specific antibodies that trigger an immune response– these can be noted on lab results as CRP and iL6. Over time, the low-grade inflammation turns into chronic inflammation and turns into metabolic diseases.

More recently, there has been evidence of reduced bacterial diversity seen in obesity. More fascinating is the Microbiome Signature you see with obesity, which is the same collective variety of bacterial species that are often seen in metabolic conditions.

At the phylum level, it was found that obese individuals had a greater firmicutes/bacteroidetes ratio than aged matched controls and this difference was reversed with either carbohydrate-restricted or fat-restricted diets.

Let’s hear what research is saying:

Most of the metabolic endotoxemia research is done on rodents and what we’re seeing is administration of antibiotics or prebiotics to genetically (ob/ob) or diet induced obese mouse models leads to a reduction in intestinal permeability and circulating plasma endotoxin.

As far as research in humans, we have a few studies to discuss. Starting with Hulson et al (2015)!

This was a study done to determine whether probiotic supplementation prevented diet-induced insulin resistance in humans. For this study, seventeen healthy individuals were randomized to a placebo group– the control group– or an intervention group who drank a probiotic twice daily for 4 weeks. They were directed to maintain normal diets for three weeks and the last week, they consumed a high fat (65%), high energy (50% greater than normal). Afterwards, the whole-body insulin sensitivity was assessed before and after overeating (via OGGT). Fasting plasma levels increased after 7 days of high-fat, high energy in the placebo group receiving no probiotic supplements, and the intervention group who received twice-a-day probiotics maintained their previous levels. Baseline glucose levels before fasting increased by 10% in the placebo group and decreased insulin sensitivity, whereas the insulin sensitivity was maintained in the probiotic group even after overeating. 

These results suggest that probiotic supplementation may be useful in the prevention of diet-induced metabolic diseases such as type II diabetes.

Next up, Vera et. al (2018)!  

In this study, there was a group of Type 2 Diabetes 81 patients divided into three-month treatment groups. He used placebo-controlled, randomized, double-blind study practices.

Group 1: followed a reduced-energy diet with a dietary portfolio (DP) comprising high-fibre, polyphenol-rich and vegetable-protein functional foods

Group 2: the other taking a placebo (P).

The primary outcome was the effect of the dietary portfolio on fecal microbiota. Secondary endpoints were biochemical parameters, lipopolysaccharide, branched-chain amino acids, trimethylamine N-oxide, glycosylated haemoglobin (HbA1c) and free fatty acids (FFAs).

The results showed patients with T2D showed intestinal dysbiosis characterized by an increase in P copri (pro-inflammatory strain of bacteria).

Furthermore, dietary intervention with functional foods significantly modified fecal microbiome compared with the placebo group by increasing microbiome diversity and modifying the abundance of specific bacteria, independently of antidiabetic drugs. Also shown in the intervention group, there was a decrease in P. copri and increases in two bacterial species known to have anti-inflammatory effects. The DP group also exhibited significant reductions in areas under the curve for glucose, total and LDL cholesterol, FFAs, HbA1c (P< 0.05), triglycerides and CRP, and an increase in antioxidant activity (P< 0.01) vs. the placebo group.

And lastly, the prebiotic study by Moludi et. al (2021):

This 12-weeks randomized, double-blind, and intervention utilized 44 patients with Coronary Artery Disease.

Group 1: assigned one probiotic capsule for 12 weeks

Group 2:placebo capsules for 12 weeks.

All the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention.

A significant decrease in IL1-Beta concentration and LPS levels was observed after the probiotic supplementation compared with the placebo.

The results indicated that participants who had ≥2.5 kg weight loss showed significantly improved cardiovascular-related factors, compared to patients with < 2.5 kg weight reduction, regardless of the supplement they took.

What can you do to repair the gut lining?

High fiber diets! Think: lots of plants, and also a large variety of plants. Our ancient ancestors used to eat over 40 different types of plants in a week! Now, we only get around 10 and we don’t really vary the variety by season as we used to. Aim for around 25g of fiber per day for optimal health. Exercise is also a great way to help your gut microbiome out by sweating out toxins. Make sure you are also getting plenty of protein for the repair of the gut lining. And finally, by taking supplements like probiotics and prebiotics, you will do your gut a favor and help replenish the good gut bacteria.

Want to address your gut health?

That is what we are here for! For further gut analysis, set up an appointment with Erin for the Gut Zoomer (https://www.vibrant-wellness.com/tests/gut-zoomer/ ) fecal test to actually see what species are in your gut! 

Looking to further optimize your health?

Empowered Nutrition specializes in one-on-one nutrition coaching! Book a free chemistry call to discuss your story and see if we’re a good fit.

Think your metabolism could some healing or a reboot? We’ve got you covered! Our Lean for Life Membership phase one and two called “Heal” and “Optimize” will help you feel empowered to reverse previous metabolic damage with the support of our team of Registered Dietitian Nutritionists. Check out our website for more details!

Enjoying the podcast?

Please review the Empowered Nutrition Podcast on Apple Podcasts or wherever you listen! Then, send me a screenshot of your positive review to podcast@empowerednutrition.health as a DM on Instagram (@empowerednutrition.health). Include a brief description of what you’re working on with your health and/or nutrition and I’ll send you a free custom meal plan!

Prefer to watch instead of listen? We’ve got you covered. You can see our livesteamed chat on our YouTube channel.

Do you have questions you would like answered on the Empowered Nutrition podcast? You can propose your questions/ideas here or reach out to me at podcast@empowerednutrition.health

Melissa’s references for this topic:

1. Boutagy, N. E., McMillan, R. P., Frisard, M. I., & Hulver, M. W. (2016). Metabolic endotoxemia with obesity: Is it real and is it relevant?. Biochimie, 124, 11–20. https://doi.org/10.1016/j.biochi.2015.06.020

2. Moludi, J., Kafil, H. S., Qaisar, S. A., Gholizadeh, P., Alizadeh, M., & Vayghyan, H. J. (2021). Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial. Nutrition journal, 20(1), 47. https://doi.org/10.1186/s12937-021-00703-7

3. Medina-Vera I, Sanchez-Tapia M, Noriega-López L, et al. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019;45(2):122-131. doi:10.1016/j.diabet.2018.09.004

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