Wednesday, May 6, 2015
A Theory Behind the Relationship Between Processed Foods and Obesity
While there has been a general slowing in the progression of global obesity, especially in the developed world, there has yet to be a reversal of this detrimental trend. A recent study has suggested that one aspect of influence regarding obesity progression lies with the consumption of foods that have incorporated emulsifiers and how they interact with intestinal bacteria including increasing the probability of developing negative metabolic syndromes in mice.1 Based on this result understanding the digestive process may be an important element to understanding how emulsifiers and emulsions may influence weight outcomes.
An emulsion is a mixture of at least two liquids where multiple components are immiscible, a characteristic commonly seen when oil is added to water resulting in a two-layer system where the oil floats on the surface of the water before it is mixed to form the emulsion. However, due to this immiscible aspect most emulsions are inherently unstable as “similar” droplets join together once again creating two distinct layers. When separated these layers are divided into two separate elements: a continuous phase and a droplet phase depending on the concentrations of the present liquids. Due to their inherent instability most emulsions are stabilized with the addition of an emulsifier. These agents are commonly used in many food products including various breads, pastas/noodles, and milk/ice cream.
Emulsifier-based stabilization occurs by reducing interfacial tension between immiscible phases and by increasing the repulsion effect between the dispersed phases through either increasing the steric repulsion or electrostatic repulsion. Emulsifiers can produce these effects because they are amphiphiles (have two different ends): a hydrophilic end that is able to interact with the water layer, but not the oil layer and a hydrophobic end that is able to interact with the oil layer, but not the water layer. Steric repulsion is born from volume restrictions from direct physical barriers while electrostatic repulsion is based on exactly its namesake electrically charged surfaces producing repulsion when approaching each other. As previously mentioned above some recent research has suggested that the consumption of certain emulsifiers in mice have produced negative health outcomes relative to controls. Why would such an outcome occur?
A typical dietary starch, which is one of the common foods that utilize emulsifiers is composed of long chains of glucose called amylose, a polysaccharide.2 These polysaccharides are first broken down in the mouth by chewing and saliva converting the food structure from a cohesive macro state to scattered smaller chains of glucose. Other more complex sugars like lactose and sucrose are broken down into their glucose and secondary sugar (galactose, fructose, etc.) structures.
Absorption and complete degradation begins in earnest through hydrolysis by salivary and pancreatic amylase in the upper small intestine with little hydrolyzation occurring in the stomach.3 There is little contact or membrane digestion through absorption on brush border membranes.4 Polysaccharides break down into oligosaccharides that are then broken down into monosaccharides by surface enzymes on the brush borders of enterocytes.5 Microvilli in the entercytes then direct the newly formed monosaccharides to the appropriate transport site.5 Disaccharidases in the brush border ensure that only monosaccharides are properly transported, not lingering disaccharides. This process differs from protein digestion, which largely involves degradation in gastric juices comprised of hydrochloric acid and pepsin and later transfer to the duodenum.
Within the small intestine free fatty acid concentration increases significantly as oils and fats are hydrolyzed at a faster rate than in the stomach due to the increased presence of bile salts and pancreatic lipase.3 It is thought that droplet size of emulsified lipids influences digestion and absorption where the smaller sizes allow for gastric lipase digestion in the duodenal lipolysis.6,7 The smaller the droplet size the finer the emulsion in the duodenum leading to a higher degree of lipolysis.8 Not surprisingly gastric lipase activity is also greater in thoroughly mixed emulsions versus coarse ones.
Typically hydrophobic interactions are responsible for the self-assembly of amphiphiles where water molecules react to a disordered state gaining entropy as the hydrophobes of the amphiphilic molecules are buried in the cores of micelles due to repelling forces.9 However, in emulsions the presence of oils produce a low-polarity interaction that can facilitate reverse self-assembly10,11 with a driving force born from the attraction of hydrogen bonding. For example lecithin is a zwitterionic phospholipid with two hydrocarbon tails that form reverse spherical or ellipsoidal micelles when exposed to oil.21 Basically emulsions could have the potential to significantly increase the hydrogen concentration of the stomach.
This potential increase in free hydrogen could be an important aspect to why emulsions produce negative health outcomes in model organisms.1 One of the significant interactions that govern the concentrations and types of intestinal bacteria is the rate of interspecies hydrogen transfer between hydrogen producing bacteria to hydrogen consuming methanogens. Note that non-obese individuals have small methanogen-based intestinal populations whereas obese individuals have larger populations where it is thought that the population of methanogen bacteria expands first before one gains significant weight.13,14 The importance behind this relationship is best demonstrated by understanding the biochemical process involved in the formation of fatty acids in the body.
Methanogens like Methanobrevibacter smithii enhance fermentation efficiency by removing excess free hydrogen and formate in the colon. A reduced concentration of hydrogen leads to an increased rate of conversion of insoluble fibers into short-chain fatty acids (SCFAs).13 Proprionate, acetate, butyrate and formate are the most common SCFAs formed and absorbed across the intestinal epithelium providing a significant portion of the energy for intestinal epithelial cells promoting survival, differentiation and proliferation ensuring effective stomach lining.13,15,16 Butyric acid is also utilized by the colonocytes.17 Formate also can be directly used by hydrogenotrophic methanogens and propionate and lactate can be fermented to acetate and H2.13
Overall the population of Archaea bacteria in the gut, largely associated to Methanobrevibacter smithii, is tied to obesity with the key factor being availability of free hydrogen. If there is a lot of free hydrogen then there is a higher probability for a lot of Archaea, otherwise there is a very low population of Archaea because there is a limited ‘food source’. Therefore, the consumption of food products with emulsions or emulsion-like characteristics or components could increase available free hydrogen concentrations, which will change the intestinal bacteria composition in a negative manner that will increase the probability that an individual becomes obese. This hypothesis coincides with existing evidence from model organisms that emulsion consumption has potential negative intestinal bacteria outcomes. One possible methodology governing this negative influence is how the change in bacteria concentration influences the available concentration of SCFAs, which could change the stability of stomach lining.
In addition to influencing hydrogen concentrations in the gut, emulsions also appear to have a significant influence on cholecystokinin (CCK) concentrations. CCK plays a meaningful role in both digestion and satiety, two components of food consumption that significantly influence both body weight and intestinal bacteria composition. Most of these concentration changes occur in the small intestine, most notably in the duodenum and jejunum.18 The largest influencing element for CCK release is the amount and level of fatty acid presence in the chyme.18 CCK is responsible for inhibiting gastric emptying, decreasing gastric acid secretion and increased production of specific digestive enzymes like hepatic bile and other bile salts, which form amphipathic lipids that emulsify fats.
When compared against non-emulsions, emulsion consumption appears to reduce the feedback effect that suppresses hunger after food intake. This effect is principally the result of changes in CCK concentrations versus other signaling molecules like GLP-1.19 Emulsion digestion begins when lipases bind to the surface of the emulsion droplets; the effectiveness of lipase binding increases with decreasing droplet size. Small emulsion droplets tend to have more complex microstructures, which produce more surface area that allow for more effective digestion.
This higher rate of breakdown produces a more rapid release of fatty acids as the presences of free fatty acids in the small intestinal lumen is critical for gastric emptying and CCK release.20 This accelerated breakdown creates a relationship between CCK concentration and emulsion droplet size where the larger the droplet size the lower the released CCK concentration.21 One of the main reasons why larger emulsions produce less hunger satisfaction is that with the reduced rate of CCK concentration and emulsion breakdown there is less feedback slowing of intestinal transit. Basically the rate at which the food is traveling through the intestine proceeds at a faster rate because there are fewer cues (feedback) due to digestion to slow transit for the purpose of digestion.
As alluded to above the type of emulsifier used to produce the emulsion appears to be the most important element to how an emulsion influences digestion. For example the lipids and fatty acid concentrations produced from digestion of a yolk lecithin emulsion were up to 50% smaller than one using polysorbate 20 (i.e. Tween 20) or caseinate.7 Basically if certain emulsifiers are used the rate of emulsion digestion can be reduced potentially increasing the concentration of bile salts in the small intestine, which could produce a higher probability for negative intestinal related events.
Furthermore studies using low-molecular mass emulsifiers (two non-ionic, two anionic and one cationic) demonstrated three tiers of TG lipolysis governed by emulsifier-to-bile salt ratio.3 At low emulsifier-bile ratios (<0.2 mM) there was no change in solubilization capacity of micelles whereas at ratios between 0.2 mM and 2 mM solubilization capacity significantly increased, which limited interactions between the oil and destabilization reaction products reducing oil degradation.3 At higher ratios (> 2 mM) emulsifier molecules remain in the adsorption layer heavily limiting lipase activity, which significantly reduces digestion and oil degradiation.3
Another possible influencing factor could be change in glucagon concentrations. There is evidence suggesting that increasing glucagon concentration in already fed rats can produce hypersecretory activity in both the jejunum and ileum.22-24 It stands to reason that due to activation potential of glucagon-like peptide-1 (GLP-1) in consort with CCK, glucagon plays some role. However, there are no specifics regarding how glucagon directly interacts with intestinal bacteria and the changes in digestion rate associated with emulsions.
The methodology behind why emulsions and their associated emulsifiers produce negative health outcomes in mice is unknown, but it stands to reason that both how emulsions change the rate of digestion and the present hydrogen concentration play significant roles. These two factors have sufficient influence on the composition and concentration of intestinal bacteria, which have corresponding influence on a large number of digestive properties including nutrient extraction and SCFA concentration management. SCFA management may be the most pertinent issue regarding the metabolic syndrome outcomes seen in mice born from emulsifiers.
It appears that creating emulsions that produce smaller drop sizes could mitigate negative outcomes, which can be produced by using lecithin over other types of emulsifiers. Overall while emulsifiers may be a necessary element in modern life to ensure food quality, instructing companies on the proper emulsifier to use at the appropriate ratios should have a positive effect on managing any detrimental interaction between emulsions and gut bacteria.
1. Chassaing, B, et Al. “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.” Nature. 2015. 519(7541):92-96.
2. Choy, A, et Al. “The effects of microbial transglutaminase, sodium stearoyl lactylate and water on the quality of instant fried noodles.” Food Chemistry. 2010. 122:957e964.
3. Vinarov, Z, et Al. “Effects of emulsifiers charge and concentration on pancreatic lipolysis: 2. interplay of emulsifiers and biles.” Langmuir. 2012. 28:12140-12150.
4. Ugolev, A, and Delaey, P. “membrane digestion – a concept of enzymic hydrolysis on cell membranes.” Biochim Biophys Acta. 1973. 300:105-128.
5. Levin, R. “Digestion and absoption of carbohydrates from molecules and membranes to humans.” Am. J. Clin. Nutr. 1994. 59:690S-85.
6. Mu, H, and Hoy, C. “The digestion of dietary triacylglycerols.” Progress in Lipid Research. 2004. 43:105e-133.
7. Hur, S, et Al. “Effect of emulsifiers on microstructural changes and digestion of lipids in instant noodle during in vitro human digestion.” LWT – Food Science and Technology. 2015. 60:630e-636.
8. Armand, M, et Al. “Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract.” American Journal of Clinical Nutrition. 1999. 70:1096e1106
9. Njauw, C-W, et Al. “Molecular interactions between lecithin and bile salts/acids in oils and their effects on reverse micellization.” Langmuir. 2013. 29:3879-3888.
10. Israelachvili, J. “Intermolecular and surface forces. 3rd ed. Academic Press; San Diego. 2011.
11. Evans, D, and Wennerstrom, H. “The colloidal domain: where physics, chemistry biology, and technology meet.” Wiley-VCH: New York. 2001.
12. Tung, S, et Al. “A new reverse wormlike micellar system: mixtures of bile salt and lecithin in organic liquids.” J. Am. Chem. Soc. 2006. 128:5751-5756.
13. Zhang, H, et, Al. “Human gut microbiota in obesity and after gastric bypass.” PNAS. 2009. 106(7): 2365-2370.
14. Turnbaugh, P, et, Al. “An obesity-associated gut microbiome with increased capacity for energy harvest.” Nature. 2006. 444(7122):1027–31.
15. Son, G, Kremer, M, Hines, I. “Contribution of Gut Bacteria to Liver Pathobiology.” Gastroenterology Research and Practice. 2010. doi:10.1155/2010/453563.
16. Luciano, L, et Al. “Withdrawal of butyrate from the colonic mucosa triggers ‘mass apoptosis’ primarily in the G0/G1 phase of the cell cycle.” Cell and Tissue Research. 1996. 286(1):81–92.
17. Cummings, J, and Macfarlane, G. “The control and consequences of bacterial fermentation in the human colon.” Journal of Applied Bacteriology. 1991. 70:443459.
18. Rasoamanana, R, et Al. “Dietary fibers solubilized in water or an oil emulsion induce satiation through CCK-mediated vagal signaling in mice.” J. Nutr. 2012. 142:2033-2039.
19. Adam, T, and Westerterp-Plantenga, M. “Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects.” Br J Nutr. 2005. 93:845–51.
20. Little, T, et Al. “Free fatty acids have more potent effects on gastric emptying, gut hormones, and appetite than triacylglycerides.” Gastroenterology. 2007. 133:1124–31.
21. Seimon, R, et Al. “The droplet size of intraduodenal fat emulsions influences antropyloroduodenal motility, hormone release, and appetite in healthy males.” Am. J. Clin. Nutr. 2009. 89:1729-1736.
22. Young, A, and Levin, R. “Diarrhoea of famine and malnutrition: investigations using a rat model. 1. Jejunal hypersecretion induced by starvation.” Gut. 1990. 31:43-53.
23. Youg, A, Levin, R. “Diarrhoea of famine and malnutrition: investigations using a rat model. 2. Ileal hypersection induced by starvation.” Gut. 1990. 31:162-169.
24. Lane, A, Levin, R. “Enhanced electrogenic secretion in vitro by small intestine from glucagon treated rats: implications for the diarrhoea of starvation.” Exp. Physiol. 1992. 77:645-648.