High–Saturated Fat Diet Increases Endotoxemia

Fat influences absorption of lipopolysaccharide

By Judy Fulop, ND, FABNO

Printer Friendly PagePrinter Friendly Page

Reference

Lopez-Moreno J, Garcia-Carpintero S, Jimenez-Lucina R, et al. Effect of dietary lipids on endotoxemia influences postprandial inflammatory response. J Agric Food Chem. 2017;65(35):7756-7763.

Objective

To determine whether long-term consumption of diets differing in the quantity and quality of fat influences postprandial intestinal endotoxin absorption. This absorption may be responsible for the postprandial inflammatory response after a high-fat meal.

Design

Randomized dietary intervention trial

Participants

This study was performed within the LIPGENE study funded by the European Union. A total of 75 participants diagnosed with metabolic syndrome completed this study.

Intervention

Participants were randomized to receive 1 of 4 isoenergetic diets for 12 weeks. Two of the diets provided 38% energy from fat: high–saturated fatty acid (HSFA) diet and high–monounsaturated fatty acid (HMUFA) diet. The remaining 2 were low-fat, high–complex carbohydrate (LFHCC) diets and provided 28% of energy as fat. One of these diets (LFHCC n-3) was supplemented with 1.24 g/d of long chain (n-3) PUFA.

After 12 weeks on the assigned diet the participants received a fat challenge in which they received 0.7 g/kg body weight of the same fat composition consumed during the dietary intervention phase.

Primary Outcome Measures

The researchers tracked plasma lipoproteins, glucose, and gene expression in peripheral blood mononuclear cells (PBMCs) and adipose tissue. Plasma levels of lipopolysaccharides (LPS) and LPS-binding protein (LBP) were determined at fasting and postprandial (4 h after a fat challenge).

Key Findings

There was a postprandial increase in LPS levels in participants who received the HSFA fat challenge (following consumption of the HSFA diet), but no postprandial changes were noted in the 3 other groups. In addition, there was a positive relationship between LPS levels and gene expression of IkBa and MiF1 in PMCs. Fasting levels of LPS did not differ between any of the diet groups after the 12-week intervention.

These results suggest that the consumption of the HSFA diet increases the intestinal absorption of LPS, which increases postprandial endotoxemia levels and the postprandial inflammatory response.

Practice Implications

This study is consistent with other studies that show that a meal high in saturated fat increases LPS transport from the gut into the serum. Interestingly, it was only after the fat challenge that significant differences became apparent between the groups, as fasting levels of LPS did not differ between any of the groups after the 12-week intervention.

This study is part of a growing number of studies that examine LPS production and transport into the serum as a mechanism that triggers inflammatory reactions caused by diet.

Shifting gut bacterial populations may be the key to shifting ‘food reactions’ and changing a potentially long list of inflammatory conditions.

Lipopolysaccharide is the major component of the outer membranes of gram-negative bacteria. It induces a strong immune response in animals and so is often used by researchers to create animal models of asthma, rheumatoid arthritis, and other immune diseases. Lipopolysaccharide, a heat-stable poison made by bacteria, was the first described endotoxin and is responsible for the consequences of certain infectious diseases.1 It binds to receptors in many cell types, but has a particular affinity for monocytes, dendritic cells, macrophages, and B-cells. Lipopolysaccharide triggers secretion of pro-inflammatory cytokines, generates superoxides, and acts as a pyrogen, causing fever.2

The generation of LPS by the gut biome is now considered an important factor in many inflammatory diseases, including autoimmunity, allergy, metabolic syndrome, obesity, diabetes, Alzheimer’s disease and a rapidly growing list of other conditions.3-7 The sudden postprandial increases in malaise and discomfort that some patients experience after eating may be caused by LPS generation by gut bacteria or, as this study suggests, increased absorption of LPS triggered by consumption of a meal high in saturated fat.

In addition intestinal derived endotoxin and the subsequent endotoxemia are now considered major predisposing factors for diseases such as atherosclerosis, sepsis, obesity and diabetes. Dietary fat in particular has been shown to increase postprandial endotoxemia.8

In 2013 Mani et al demonstrated that meals rich in saturated fatty acids (coconut oil) increased postprandial endotoxin level concentrations in pigs while meals high in omega-3 PUFA fish oils lowered endotoxin levels by half. Olive oil and other vegetable oils had no impact.8 Whether coconut oil has a similar endotoxic effect in humans is not yet clear. Still this knowledge should caution us about the use of coconut oil and other saturated fats in patients who we suspect suffer from endotoxemia.

In recent years the gut microbiome has come to be seen as a contributor to the pathogenesis of obesity and type 2 diabetes mellitus. Thus manipulation of the human gut microbiota may soon become a therapeutic target for diabetes.9 It appears that LPS production is the mediator that increases gut permeability and may trigger this disease. In type 2 diabetes, LPS elicits a milder “hyporesponsive” immune response and this may be why diabetics are prone to infections and have such difficulty fighting them.10

Brian Mcfarlin et al reported in August 2017 that supplementation with a combination probiotic was useful at lowering endotoxemic postprandial reactions. The participants in his study (N=75) were screened and selected for having strong endotoxemic postprandial reactions, at least a 5-fold postprandial LPS increase over their preprandial level. Participants were randomized to receive either a rice flour placebo or a combination spore-forming probiotic (Bacillus indicus [HU36], B subtilis [HU58], B coagulans, B licheniformis, and B clausii) for 30 days. Use of the probiotics was associated with a significant 42% reduction in endotoxins and a 24% reduction in triglycerides.11 The placebo was associated with a significant 36% increase in endotoxin levels, making this reader wonder about the safety of uncooked rice flour and its impact on gut biome.

A number of other studies, in vitro and in mice, suggest various other probiotics may also be useful in reducing LPS-induced inflammatory reactions, at least in part by maintaining intestinal integrity.12

The growing knowledge base about LPS should have us rethinking some of our previous assumptions. Food-related reactions that we have thought were allergic could actually be secondary to endotoxin production or increased absorption from high–saturated fat meals. The “Candida die-off reactions” that some people attribute to coconut oil consumption may, in reality, be increased endotoxin absorption. Shifting gut bacterial populations may be the key to shifting “food reactions” and changing a potentially long list of inflammatory conditions.

About the Author

Judy Fulop, ND, FABNO is a naturopathic physician who has been practicing naturopathic medicine at the Osher Center for Integrative Medicine at Northwestern in Chicago, Illinois for the past 17 years. She is also an adjunct professor, teaching year-round in the Naturopathic Medical program at the National University of Health Sciences in Lombard, Illinois. Fulop is a popular speaker at medical conferences and conferences for the public.

References

  1. Hitchcock P, Leive L, Makela H, Rietschel ET, Strittmatter W, Morrison DC. Lipopolysaccharide nomenclature--past, present, and future. J Bacteriol. 1986;166(3):699-705.
  2. Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK. Aldose reductase mediates the lipopolysaccharide-induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem. 2006;281(44):33019-33029.
  3. Feehley T, Belda-Ferre P, Nagler CR. What's LPS got to do with it? A role for gut LPS variants in driving autoimmune and allergic disease. Cell Host Microbe. 2016;19(5):572-574.
  4. Munford RS. Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect Immun. 2008;76(2):454-465.
  5. Hersoug LG, Møller P, Loft S. Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity. Nutr Res Rev. 2018:1-11.
  6. Harsch IA, Konturek PC. The role of gut microbiota in obesity and type 2 and type 1 diabetes mellitus: new insights into "old" diseases. Med Sci (Basel). 2018;6(2). pii: E32.
  7. Wang LM, Wu Q, Kirk RA, et al. Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat brain. Am J Nucl Med Mol Imaging. 2018;8(2):86-99.
  8. Mani V, Hollis JH, Gabler NK. Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond). 2013;10(1):6.
  9. Sato J, Kanazawa A, Watada H. Type 2 diabetes and bacteremia. Ann Nutr Metab. 2017;71 (Suppl 1):17-22.
  10. Khondkaryan L, Margaryan S, Poghosyan D, Manukyan G. Impaired inflammatory response to LPS in type 2 diabetes mellitus. Int J Inflam. 2018;2018:2157434.
  11. McFarlin BK, Henning AL, Bowman EM, Gary MA, Carbajal KM. Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World J Gastrointest Pathophysiol. 2017;8(3):117-126.
  12. Cui Y, Liu L, Dou X, et al. Lactobacillus reuteri ZJ617 maintains intestinal integrity via regulating tight junction, autophagy and apoptosis in mice challenged with lipopolysaccharide. Oncotarget. 2017;8(44):77489-77499.