Why Weight Loss Programs Fail

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The common belief in the health industry is that obesity is the result of overfeeding due to lack of self-control. The idea is that weight fluctuations can be controlled by simply balancing and manipulating caloric intake against energy expenditure. And while the increased consumption of processed sugary and fatty foods lends validity to this concept, research reveals that there is much more to obesity than “calories in versus calories out”.

Over 1.9 billion people worldwide are overweight or obese, but it may not be due to their caloric intake (1). In fact, hormones, inflammation, neural pathways, and the mucosal lining of the gastrointestinal tract have a complex and interdependent relationship in the development of obesity. Obesity is a disease, and like any other disease, it has a specific pathology that goes beyond poor habits. Traditional treatments for obesity include: calorie restriction, vigorous exercise, and in some cases, pharmaceutical and surgical approaches. However, current research suggests that restoring health to the gut may hold the key to resolving the obesity epidemic.

Obesity as an Inflammatory Disorder

The mucosal lining of the human intestines is the first line of defense for the immune system. Epithelial tight junctions and a thick mucosal layer work together to keep harmful microbes out of the bloodstream, while allowing nutrients to pass through. Several diet and lifestyle factors associated with a Western lifestyle can cause this highly selective system to malfunction.These factors include antibiotics, physical and psychological stress, and high-fat, high-sugar diets.  

High-fat diets in particular appear to be more problematic – not because dietary fat increases body fat but because the research shows that dietary fats can be more damaging to the gut microbiome (2). The majority of the gut microbiome is made up of gram-negative bacteria that utilize dietary fatty acids to create endotoxins in their outer cell membranes (3). The primary endotoxin of concern is called lipopolysaccharide, or LPS. When bacterial cells are whole, LPS is used for cell-to-cell communication with other bacteria. However, when these gram-negative bacteria die, they release LPS into the intestinal lumen, where they have the potential to trigger inflammation.

Since these gram-negative bacteria can utilize a variety of fatty acids, one study published in Nutrition & Metabolism set out to explore the effects that dietary fats can have on the toxicity of LPS. Interestingly, they found that saturated fats, particularly coconut oil, produced the most toxic form of LPS, while omega-3 unsaturated fatty acids actually reduced the toxicity of LPS in the lumen (2). When LPS enters circulation, it can interact with adipocytes and induce morphological changes in the fat cells, including increasing the volume of fat cells. In addition, circulating LPS can trigger a cascade of low-grade inflammatory reactions anywhere in the body.

Since diet plays a significant role in the development of inflammatory conditions like obesity, it is common to think of self-control as an obvious solution. However, there may be more to overeating than a simple lack of willpower.

A recent study published in July 2018 in the Journal of Pathophysiology tested the intestinal barrier function of 122 obese and non-obese patients. Results indicated that obese patients had impairments in their tight junctions – the proteins that stitch intestinal cells together – and increased serum levels of zonulin and LPS-binding protein, two biomarkers of intestinal barrier dysfunction (4). Supporting research suggests that this intestinal hyperpermeability and the resulting endotoxic response can actually lead to overeating by hindering the body’s ability to accurately assess hunger and satiety (5).

Vagal Afferent Nerve and Satiety

The digestive tract is a very intuitive system that relies heavily on specific feedback to regulate metabolism and initiate digestion and absorption (5). The primary neural pathway involved in this system  is known as the vagal afferent nerve, or VAN. This bidirectional neural pathway has receptors throughout the entire GI tract and delivers signals between the brain and the gut in response to the presence or absence of food (5).

The VAN also expresses several receptors for satiety and hunger hormones, such as leptin and ghrelin. Leptin is the satiety hormone released from adipose tissue and gastric mucosa that communicates to the hypothalamus that the stomach is full. Ghrelin, on the other hand, is the hunger hormone released from the gastric mucosa in the absence of food.

Multiple studies suggest that LPS can damage the VAN, resulting in leptin resistance. Leptin resistance occurs when the hypothalamus does not receive the signal of satiety despite elevated circulating leptin levels (6). In rodent studies, researchers found that high-fat diets increased LPS and increased serum leptin levels which lead to weight gain and leptin resistance in the VAN, specifically on the arcuate nucleus (7). Similarly, studies have shown that rodents treated with low dose concentrations of LPS for 6 weeks also developed leptin resistance in VAN (8).

In addition to leptin resistance, LPS can also lead to insulin resistance, another hormone that regulates satiety in the hypothalamus. In a study published in the International Journal of Molecular Science, rodents that received LPS became unresponsive to insulin and, as a result, did not experience satiety (9). This research suggests that overeating might be a self-perpetuating feedback loop that starts in the gut and dramatically affects the brain. In this way, overeating is not merely an issue of self-control but rather an integral piece in the pathophysiology of obesity.

Since obesity starts with an imbalance in gut microbiota – that ultimately leads to LPS translocation, chronic inflammation, and afferent nerve dysfunctiontreating obesity must involve a multi-faceted approach aimed at restoring health and balance to the gut.

Step 1: Neutralize toxins

Secretory immunoglobulin A (sIgA) is the body’s first line of defense against toxins like LPS in the intestinal lumen. Immunoglobulins, also known as antibodies, can reduce the toxic load on the system by binding to antigens and removing them from the system. Serum-derived bovine immunoglobulins (SBI) can assist in lightening the toxic load on the body. As a dairy-free alternative to colostrum, SBI powders can bind a variety of pathogens, including bacteria, viruses, and fungi, as well as their toxic by-products, and remove them from the body (10).

Step 2: Recondition the gut

Studies investigating microbial diversity have identified a handful of species as next-generation beneficial bacteria that appear to protect the human host. These bacterial species include Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bifidobacterium spp.

A. muciniphila is a mucin-degrading bacterium that plays a crucial role in the regulation of the gut barrier and metabolism (11). The gut barrier consists of the intestinal lining coated in a thick layer of mucus to keep unwanted toxins and pathogens out of the bloodstream. In humans, A. muciniphila is associated with healthier metabolic status, particularly improved insulin sensitivity and glucose homeostasis, and better outcomes after weight loss (12). Low abundance of A. muciniphila has been linked to obesity, diabetes, liver disease, cardiometabolic diseases, and low-grade inflammation (13).

F. prausnitzii is one of the most abundant and important commensal organisms of the human gut microbiota. In light of recent findings, F. prausnitzii is quickly becoming known as an anti-inflammatory bacterium that regulates human intestinal health. Low levels of this bacteria have become common signatures of intestinal disorders like IBD, IBS, colorectal cancer, obesity, and celiac disease (14).

The genus Bifidobacterium plays an important role in maintaining barrier function and stimulating the immune system (15). Because Bifidobacteria are also butyrate-producers, they can help reduce intestinal inflammation and also appear to help with weight management (16). Low levels of Bifidobacteria have been associated with obesity, diabetes, celiac disease, allergic asthma, dermatitis, IBD, chronic fatigue syndrome, and psoriasis (17-19).

However, as anaerobic bacteria, F. prausnitzii and A. muciniphila are impossible to take as probiotic supplements. Instead, the only way to increase their abundance is from within – by feeding it the right prebiotics. Fortunately, Bacillus spores and Precision Prebiotics have been shown to significantly increase populations of these three keystone bacteria in the gut. Precision Prebiotics are functional fibers that include fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), and xylo-oligosaccharides (XOS) found in lentils, peas, bamboo shoots, corn cobs, kiwifruit, cow’s milk, and honey.

FOS derived from kiwifruit increased the abundance of F. prausnitzii by 100% in 4 weeks (20). Another study published in Diabetes found that FOS supplementation was correlated with an 8,000% increase in A. muciniphila in only 5 weeks (21). XOS derived from corn cobs increased the abundance of Bifidobacteria by 21% in as little as 4 weeks, and GOS derived from lactose increased the abundance of Bifidobacteria by 66% in just 7 days (22-23). Increasing populations of these protective bacteria is an integral part of reconditioning and reinforcing a healthy gut microbiome.

Step 3: Rebuild mucosal barrier

The mucosa is a key barrier that protects LPS from entering into the basolateral layer. When the mucosa suffers from inadequate production of MUC2 mucin and inadequate viscosity, it fails to perform its barrier function and thus allows for the migration of LPS.

MUC2 mucin is a protein that gives the inner mucus layer its thick, gel-like qualities. Increasing MUC2 mucin production can help prevent LPS and other toxins from migrating towards the intestinal epithelial and triggering an innate immune reaction. Butyrate appears to stimulate MUC2 mucin production in the gut, and amino acids L-threonine, L-serine, L-proline, and L-cysteine act as the essential building blocks necessary for rebuilding a healthy, dense mucosal barrier (24).

Together, these 3 steps can help to significantly restore the health of the gut microbiome and reduce the risk of developing inflammatory conditions like obesity.


  1. “Obesity and Overweight.” World Health Organization. URL: www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
  2. Mani V, Hollis JH, Gabler NK. Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond). 2013;10(1):6.
  3. Boutagy NE., et al. Metabolic Endotoxemia with Obesity: Is It Real and Is It Relevant? Biochimie. 2016;124: 11–20.
  4. Genser L et al. Increased Jejunal Permeability in Human Obesity Is Revealed by a Lipid Challenge and Is Linked to Inflammation and Type 2 Diabetes. J Pathol. 2018.
  5. De Lartigue G, et al. Vagal Afferent Neurons in High Fat Diet-Induced Obesity; Intestinal Microflora, Gut Inflammation and Cholecystokinin. Physiology & Behavior. 2011;105(1):100-105.
  6. De Lartigue G, et al. Diet-Induced Obesity Leads to the Development of Leptin Resistance in Vagal Afferent Neurons. Am J Physiol Endocrinol Metab. 2011;301(1):e187-195.
  7. De Lartigue G, et al. Deletion of Leptin Signaling in Vagal Afferent Neurons Results in Hyperphagia and Obesity. Molecular Metabolism. 2014;3(6):595-607.
  8. De La Serre CB, et al. Chronic Administration of Microbial Lipopolysaccharide Results in Leptin Resistance in Vagal Afferent Neurons, Hyperphagia and Increased Body Weight in Rats. Gastroenterology. 2011;140(5).
  9. Rorato R, et al. LPS-Induced Low-Grade Inflammation Increases Hypothalamic JNK Expression and Causes Central Insulin Resistance Irrespective of Body Weight Changes. Int J Mol Sci. 2017;18(7): p1431.
  10. Detzel CJ, Horgan A, Henderson AL, et al. Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model. PloS one. 2015;10(4):e0120278.
  11. Chelakkot C, et al. Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp & Molecular Med. 2018;50:e450
  12. Dao MC, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65:426-436.
  13. Schneeberger M, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Scientific Reports. 2015; 5:16643.
  14. Martin R, Miquel S, Benevides L, et al. Functional Characterization of Novel Faecalibacterium prausnitzii Strains Isolated from Healthy Volunteers: A Step Forward in the Use of F. prausnitzii as a Next-Generation Probiotic. Front Microbiol. 2017; 8: 1226.
  15. Picard C, et al. Review article: bifidobacteria as probiotic agents – physiological effects and clinical benefits. Aliment Pharmacol Ther.  2005;22:495–512.
  16. Stenman LK, et al. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Benef Microbes. 2014;5(4):437-445.
  17. Collado MC, et al. Imbalances in fecal and duodenal Bifidobacterium species composition in active and non-active celiac disease. BMC Microbiol. 2008;8:232.
  18. Gao X, et al. Obesity in school-aged children and its correlation with gut E. coli and Bifidobacteria: a case-control study. BMC Pediatr. 2015;15:64.
  19. Akay HK, et al. The relationship between bifidobacterial and allergic asthma and/or allergic dermatitis: a prospective study of 0-3-year-old children in Turkey. Anaerobe. 2014;28:98-103.
  20. Blatchford P, Stoklosinski H, Eady S, et al. Consumption of kiwifruit capsules increases Faecalibacterium prausnitzii abundance in functionally constipated individuals: a randomised controlled human trial. J Nutr Sci. 2017; 6: e52.
  21. Everard A, Lazarevic V, Derrien M, et al. Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice. Diabetes. 2011 Nov; 60(11): 2775–2786.
  22. Finegold SM, et al. Xylooligosaccharide increases bifidobacteria but not lactobacilli in human gut microbiota. Food Funct. 2014;5(3):436-45.
  23. Depeint F, et al. Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind, crossover, placebo-controlled intervention study 1–3. Am J Clin Nutr. 2008;87(3):785-91.
  24. Faure M, Mettraux C, Moennoz D, et al. Specific Amino Acids Increase Mucin Synthesis and Microbiota in Dextran Sulfate Sodium–Treated Rats. J Nutr. 2006 Jun;136(6):1558-64.

Comments 5

  1. Jean,
    Will you please clarify the protocol for the three products you have mentioned above. Do you suggest to start with one product and then continue step by step – 3 month program. In what order please. Thank you in advance.

    1. One before the other. They can be taken together, but it’s better to separate them in case you don’t tolerate one well. It makes it easier to determine the culprit.

    1. The products are MegaSporeBiotic for 4 weeks. MegaPreBiotic for 4 weeks. MegaMucosa for 4 weeks.

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