The Role of Probiotics and Prebiotics in Metabolic Syndrome

Antoaneta Sawyer, Ph.D.

The USDA statistics show that since 1970, average daily calorie intake in the U.S. has increased by nearly 25 percent. Researchers at Cornell University examined 52 of the well known painting “The Last Supper” and more than 1,000 years separated the earliest painting from the most modern one . Their report in The International Journal of Obesity (April, 2010), shows that the plate size and entrée size enlarged by about two-thirds over the millennium while bread size increased by nearly 25 percent. At the same time the World Health Organization (WHO) estimations are that by 2015, there will be more than 1.5 billion overweight consumers, with an incurring health cost beyond $117 billion per year in the US alone. Thus, the needs of future research in the science of metabolomics as well as the opportunity for scientifically-substantiated weight management products for food control are strongly increased.
The new science of metabolomics is constantly discovering new mechanisms to control morbid obesity as part of the metabolic syndrome. Recently it was found a new connection between obesity as part of the metabolic disorder related to the use of probiotics and probiotics, as regulators of the gut microflora (microbiota) in relevance with the food intake control. Results from this study suggest that there is a significant decrease in body mass index (BMI), linked to a modulation of gut peptides and appetite modulation that have been observed upon long term treatment of overweight and obese patients with pro-and prebiotics. The researchers also note that the concept may also be applicable to humans. “Moreover, the metabolomic analysis will allow to select the potential new microbial targets related to obesity and related disorders in the future” (Delzenne & Cani).
Matsusawa (2007) writes,” Recently, adipocytes have been shown to be recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines, among which, adiponectin, a newly found adipose tissue-specific collagen-like protein has been noted as an important antiatherogenic and antidiabetic protein and then proceeds. “Visceral fat accumulation causes dysfunction of adipocytes and results in the development of a variety of metabolic and circulatory diseases through the abnormal secretion of adipocytokines.” Hotamisligil agrees that adipose tissue may produce increased levels of cellular, hormone-like substances—cytokines and other bioactive substances referred to as adipocytokines (Hotamisligil, 2004). As a result of the above vicious circle, insulin sensitivity in organs like muscle and liver is decreasing (Matsuzawa, Funahashi, Kihara & Shimomura, 2004). It is also hypothesized that secondary factors as nonesterified fatty acid liberation and adipokine (e.g., adiponectin) production (Carr et al., 2004) as well as other risk factors (Egan & Julius, 2004; Janssen, Debets, Leenders & Smits, 2002) may also play a major role in metabolic syndrome pathogenesis.
There are findings that raise the question that gut residential microflora may play an important role in regulating weight as a factor in obesity development (Furtado, 2010). The human gut includes 100 billion microorganisms per milliliter, with a total of 100 trillion microorganisms residing in the GI tract. It is obvious that our bodies have more bacteria than cells, while comparing with the estimated 10 trillion cells in the human body. An adult human’s GI tract contains approximately 1012 microorganisms per milliliter of luminal content, with at least between 15,000 and 36,000 distinct species of bacteria. Gut microorganisms, also termed “microbiota” are the trillions of bacteria that normally reside in the human GI tract, and affect nutrient absorption and energy regulation. While the term “microbiota” is defined as a collection of microorganisms normally associated with a particular tissue or organ while “microbioma” is defined as the collection of the microbial genomes (Gill, Pop & De Boy, 2006).
Two main divisions of beneficial bacteria—Bacteroides and Firmicutes—are known as normal residents in the gut, and the equilibrium of the two is very important in determining an individual’s propensity for obesity. A study found an association between obesity and an increased relative abundance of Firmicutes, compared with Bacteroides and that lean people show different gut flora than those who are overweight or obese (Bajzer & Seeley, 2006). Another research investigating the gut bacterial flora of obese mice and humans has discovered fewer Bacteroides and more Firmicutes than lean counterparts, suggesting differences in caloric extraction of ingested food substances due to the composition of the gut microflora (Di Baise, Zhang, Crowell et al., 2008). Thus, obesity it is not so much explained with overeating, but as to the different metabolic activities of already modified gut flora facilitating the extraction of calories from ingested dietary substances while storing calories in adipose tissue for later use. It is obvious that there is an elevated rate of food ingestion. Therefore, modulating the equilibrium or gut microflora may have a role in the future prevention and treatment of obesity.
Probiotics are nonpathogenic live microorganisms that are believed to confer health benefits to the host when ingested (WHO). In authors’ proper statements “The role of the gut microflora in affecting calorie control and satiety is gradually being unravelled” (Gibson, 2010). Authors’ conclusions are that prebiotics may beneficially modify bacterial populations in our guts and aid weight management, with “promising effects also shown in humans.” As has been suggested from the above studies, lean invidividuals possess more Bacteroides and those with obesity possess more Firmicutes (Ley, Turnbaugh, Klein, & Gordon, 2006). Kalliomäki, Collado, Salminen & Isolauri (2008) established the rule that early gut microbiota composition can guide weight development throughout early childhood.
Ingestion of probiotics is recommended even as preventative approach to maintaining the balance of the intestinal microflora and thereby enhancing health and well being (Furtado, 2009). A survey of the literature indicates positive results in over 50 human clinical trials, with prevention/treatment of infections the most frequently reported output (Gorbach, 2000). Increased levels of probiotics may induce a “barrier” influence against common pathogens. Mechanisms of effect are likely to include excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation, and formation of specific antimicrobial agents (Fooks & Gibson, 2002).
Researchers have suggested that improved immunity and weight loss or antiobesity prevention are among some of their multiple benefits. There are many “in vivo” and “in vitro” trials on the anti-obesity effect of Lactobacillus rhamnosus (L. rhamnosus), a bacterium that produces conjugated linoleic acid (CLA). It was found that after eight weeks of oral feeding with L. rhamnosus, mice lost weight without reducing their energy intake. CLA has been suggested to possess a number of potential health benefits based on animal studies, including the ability to reduce body fat. Anyway, this is just one of the mechanisms in which probiotics are believed to show their antiobesity effects.
Recent study suggests a compelling role for probiotics in enhancing liver health, in case of nonalcoholic fatty liver steatosis or disease (NAFLD) (O’Sullivan, 2008). Liver steatosis has long been associated with long-term and excessive alcohol consumption, but there is other -- "nonalcoholic" version of the disease that is believed to be caused by a poor diet, loaded with simple sugars and complex carbohydrates. Called a “non-alcoholic fatty liver disease” (NAFLD), or liver steatosis, the disorder affects about a third of the American adult population and numbers are progressively rising. Patients are unaware they have the above problem, as it rarely causes symptoms by itself, but when accelerates in its progression- it can lead to serious liver damage and to final death. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis as concluded in a study by Biddinger et al. (2008). Sedentary lifestyles, consumption of energy-rich diet, obesity, and advanced age are important reasons for this rise. According to a study done by Duke University Study (DUS, 2003) people with metabolic syndrome who made intensive lifestyle modifications had a 47% reduction in insulin overproduction, also known as hyperinsulinemia and caused by insulin resistance. Those who exercised but didn’t lose weight saw a 27% reduction (DUS, 2003).
Although the causative link between central body fat and insulin resistance has not been proven yet, numbers of factors are now under clinical trials: i.e., increased levels of fatty acids in the blood, fat derived hormones and cytokines, and abnormalities in the brain's interpretation and coordination of metabolic cues (Eckel et al., 2005). Intestinal microflora is believed to play a large role in the progression from NAFLD to real cirrhosis of the liver. According to the same study, when gut flora is high in facultative microbes (e.g., Enterobacteriaceae) and low in anaerobes (e.g., Bifidobacteria), higher levels of ammonia and endotoxins result. Probiotics have been shown to modulate intestinal flora and increase the anaerobic population. The era of microgenomics is now providing tools to more effectively understand probiotics mechanism of action in the gut area.
Prebiotics are non-digestible oligosaccharides believed to act as “fertilizers” of the colonic microflora, enhancing growth of beneficial residential organisms (e.g. Bifidobacterium, Lactobacillus) (WHO). Prebiotics are believed to offer health benefits on the host, explained with the activation or modulation of lipid metabolism in general. Researchers have even suggested potential "antiobesity" effects as well, possibly by modulating gut hormones, such as the peptide YY (PYY) and the glucagon-like peptide-1(GLP-1). Inulin and oligofructose (naturally occurring fructooligosaccharides [FOS]) are prebiotics that are gaining more exposure lately as possible health-enhancing agents. Prebiotics modulate the lipid metabolism, most likely via the process of fermentation (Furtado, 2009).
The combination of prebiotics and probiotics, known as "synbiotics", is advised to be ingested as it is believed to show enhanced health benefits acting as a “functional food.” Several articles review the synergistic role of prebiotics and probiotics on obesity and discuss research that suggests that individuals with obesity may have differing amounts of particular microbiota (e.g. Firmicutes) The combination of pre-and probiotics, has been proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for health-enhancing, functional food ingredients that are able of modifying the gut flora to its beneficial ratio (Gibson & Roberfroid, 1995)
New science breakthrough article published in Nature (Ley, Turnbaugh, Klein & Gordon, 2006) reported that microbial populations gut flora is different between obese and lean people and that obese people are losing weight when probiotics are added. The breakthrough is in the finding that obese people microflora reverted back to the one of the lean people, suggesting that obesity may have a microbial pathogenesis component. Despite known as “non-digestible” prebiotics are between the food fibres or ingredients that have a beneficial effect through their selective metabolism in the intestinal tract” (Gibson et al., 2004).
“The role of the gut microflora in affecting the caloric intake control and satiety is gradually being unravelled” are the statements of Prof. Glenn Gibson (University of Reading). According to a new review at the catholic university of Louvain (Belgium) in the metabolic disorder area “in vivo” animal data supported the potential of prebiotics to beneficially manage metabolic syndrome and other metabolic derangements in overweight or obese patients (International Dairy Journal). The scientists note that “inulin-type” prebiotics may reduce appetite, increase satiety, and thereby decrease the amount of energy consumed. However, such effects were only noted after several weeks and no such effects being observed over a 48-hour period.
Although researchers have been utilizing the science of genomics to make strides in gut microbiota research, there are many questions that must be answered in the future e.g:
1. Could the elimination of obesity-related bacteria virtually eliminate obesity?
2. Are differences in gut flora in lean individuals versus overweight or obese the cause or the consequence of obesity?
3. What are the hormones that direct changes in the gut flora and in which degree they can be modulated by probiotics and prebiotics?
4. What are the exact proportions of Bacteroides and Firmicutes that are beneficial in humans?
5. Could gut genomic research one day make surgery obsolete?
As a final conclusion it seems that probiotics and prebiotics are able to modify the gut microbiota in a positive way. Some of the modifications of the gut flora include an increase in the production of hormones that may have weight loss properties; others may be helpful in terms of decreasing inflammation, so it appears prudent to include them as part of a healthy, balanced diet.
REFERENCES:
1. Lee, H. Park, J. H., Seok, S. H.(2006).Human originated bacteria. Lactobacillus rhamnosus PL60 produces conjugated linoleic acid and shows anti-obesity effects in diet-induced obese mice. Biochem Biophys Acts, 1761, 736–44.

2. Gorbach, S. L. (2000). Probiotics and gastrointestinal health. Am J Gastroenterol, 95, 2

3. Fooks, L. J., Gibson, G. R. (2002). Probiotics as modulators of the gut flora. Br J Nutr, 88, 39–49.

4. O’Sullivan, D. J. (2008). Genomics can advance the potential for probiotic cultures to improve liver and overall health. Curr Pharm Des, 4, 1376–8.

5. Celleno, L., Tolaini, M. V., D’Amore, A., et al.(2007). A dietary supplement containing standardized Phaseolus Vulgaris extract influences body composition of men and women. Int J Med Sci, 4, 45–52.

6. Roberford, M. B. (2002). Functional foods: concepts and application to inulin and oligofructose. Br J Nutr. 87, 139–43.

7. Keenan, M. J., Zhou, J., McCutcheon, K. L. et al.(2005).Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat. Br J Nutr, 94, 1–11.
8. Gibson, G. R. & Roberfroid, M. B. (1995).Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr, 125, 1401–12.

9. Gill, S. R., Pop, M., DeBoy, R. T., et al.(2006).Metagenomic analysis of the human distal gut microbiome. Science. 312, 1355–9.

10. Amann, R. I., Ludwig, W. & Schiefer, K. H.(1995). Phylogenic identification and in-situ detection of individual microbial cells without cultivation. Microbiol Rev, 59, 143–69.

11. Berg, R. D. (1996). The indigenous gastrointestinal microflora. Trends Microbiol 4, 430–5.

12. Bajzer, M. & Seeley, R. J. (2006). Physiology: obesity and gut flora. Nature, 444, 1009–10.

13. DiBaise, J. K., Zhang, H., Crowell, M. D., et al. (2008). Gut microbiota and the possible relationship with obesity. Mayo Clin Proc. 83, 460–9.

14. Bäckhed, F., Ding, H., Wang, T., et al. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A, 101, 15718–23.

15. Ley, R. E., Bäckhed, F., Turnbaugh, P., et al.(2005).Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A, 102, 11070–5.

16. Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444, 1022–3.

17. Kalliomäki, M., Collado, M. C., Salminen, S., & Isolauri, E. (2008). Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr, 87, 534–8.

18. Furtado, M. (2009). Probiotics, Prebiotics, Gut Microbiota, and Obesity Bariatric. Times 6, 27–30.
19. Zhang, H., DiBaise, J. K., & Zuccolo, A. (2009). Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 106, 2365–70.
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