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Relation
Lopez-Moreno J, Garcia-Carpintero S, Jimenez-Lucina R, et al. The effect of dietary lipids on endotoxemia influences the postprandial inflammatory response.J Agric FoodChem. 2017;65(35):7756-7763.
Objective
To determine whether long-term consumption of diets varying in the amount and quality of fat affects postprandial intestinal endotoxin absorption. This absorption may be responsible for the postprandial inflammatory response following a high-fat meal.
Draft
Randomized dietary intervention trial
Participant
This study was conducted as part of 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: the high saturated fatty acid (HSFA) diet and the 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, 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 fasting and postprandial (4 h after fat challenge).
Key insights
There was a postprandial increase in LPS levels in participants receiving the HSFA fat challenge (after consuming the HSFA diet), but no postprandial changes were noted in the 3 other groups. Furthermore, there was a positive relationship between LPS levels and IkBa and MiF1 gene expression in PMCs. Fasting levels of LPS did not differ between any of the diet groups after the 12-week intervention.
These results suggest that consumption of the HSFA diet increases intestinal absorption of LPS, which increases postprandial endotoxemia levels and the postprandial inflammatory response.
Practice implications
This study is consistent with other studies showing that a meal high in saturated fat increases LPS transport from the intestine to the serum. Interestingly, significant differences between the groups only emerged after fat loading, as fasting levels of LPS did not differ in any of the groups after the 12-week intervention.
This study is part of a growing number of studies investigating LPS production and serum transport as a mechanism triggering diet-induced inflammatory responses.
Shifting gut bacterial populations may be key to shifting “food responses” and altering a potentially long list of inflammatory conditions.
Lipopolysaccharide is the main component of the outer membranes of gram-negative bacteria. It induces a strong immune response in animals and is therefore often used by researchers to create animal models of asthma, rheumatoid arthritis and other immune diseases. Lipopolysaccharide, a heat-stable bacterial toxin, was the first endotoxin described and is responsible for the consequences of certain infectious diseases.1It binds to receptors in many cell types, but has a particular affinity for monocytes, dendritic cells, macrophages and B cells. Lipopolysaccharide triggers the secretion of pro-inflammatory cytokines, produces superoxides, and acts as a pyrogen, causing fever.2
The production of LPS by the gut biome is now recognized as an important factor in many inflammatory diseases, including autoimmunity, allergies, metabolic syndrome, obesity, diabetes, Alzheimer's disease and a rapidly growing list of other diseases.3-7The sudden postprandial increase in malaise and discomfort that some patients experience after eating may be caused by the production of LPS by gut bacteria or, as this study suggests, by increased absorption of LPS triggered by consumption of a meal high in saturated fats.
In addition, gut-derived endotoxin and 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. showed that meals rich in saturated fatty acids (coconut oil) increased postprandial endotoxin concentrations in pigs, while meals high in omega-3 PUFA fish oil reduced endotoxin concentrations by half. Olive oil and other vegetable oils had no effect.8It is not yet clear whether coconut oil has a similar endotoxic effect in humans. Nevertheless, this knowledge should caution us against the use of coconut oil and other saturated fats in patients we suspect of suffering from endotoxemia.
In recent years, the gut microbiome has been considered a contributor to the pathogenesis of obesity and type 2 diabetes mellitus. Therefore, manipulating the human gut microbiota may soon become a therapeutic target for diabetes.9It appears that LPS production is the mediator that increases intestinal permeability and may trigger this disease. In type 2 diabetes, LPS triggers a milder "hyporesponsive" immune response, and this may be why diabetics are susceptible to infections and have such difficulty fighting them.10
Brian Mcfarlin et al. reported in August 2017 that supplementation with a combined probiotic was useful in reducing endotoxemic postprandial reactions. Participants in his study (N = 75) were screened and selected for strong endotoxemic postprandial responses, 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 of spore-forming probiotic (Bacillus indicus[HU36],B subtilis[HU58],B-coagulants,B. licheniformisandB clausii) for 30 days. Use of the probiotics was associated with a significant 42% reduction in endotoxins and a 24% reduction in triglycerides.11The placebo was associated with a significant 36% increase in endotoxin levels, leading this reader to wonder about the safety of uncooked rice flour and its effects on the gut biome.
A number of other studies, in vitro and in mice, suggest that various other probiotics may also be useful in reducing LPS-induced inflammatory responses, at least in part by maintaining intestinal integrity.12
The growing knowledge base about LPS should cause us to reconsider some of our previous assumptions. Food-related reactions that we thought were allergic may actually be secondary to endotoxin production or increased intake from highly saturated fat meals. The “Candida die-off” reactions that some people attribute to coconut oil consumption may actually be increased endotoxin intake. Shifting gut bacterial populations may be key to shifting “food responses” and altering a potentially long list of inflammatory conditions.