A Quick Taste
Elie Metchnikoff, working at the Pasteur Institute in Paris in the early 1900s, was one of the first scientists to recognize that the types of bacteria (microbiota) residing in our gut have a significant impact on our overall health.1 He noted that increasing the content of lactic acid producing bacteria, through the consumption of soured milk products, contributed to increased well-being.1 Today it is common for people to consume live lactic-acid bacteria as supplements or in foods for their potential health benefits (probiotics).2 Another way to promote the growth of beneficial microbes is to consume foods (prebiotics) that contain “selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health.”3 This article summarizes the emerging data suggesting that soy products may promote a healthy gut microbiota.
Gut microbiota play a critical role in human metabolism and health by processing nutrients and drugs, synthesizing vitamins and inhibiting growth of potential pathogen. The gut microbiota co-evolved with humans in a symbiotic manner, so that those microbes that thrive on ingredients in the human diet serve to provide additional metabolic activity to the host (gut microbiota have 100 times more genes than human), thereby enhancing nutrient availability while also affording protection against opportunistic pathogens. The large intestine harbors most of the gut microbiota and is the major site for fermentation of dietary ingredients which are not efficiently digested in the small intestine. The efficient extraction of energy from the diet made possible by the metabolic activity of the colonic microbiota, in some cases, has undesirable consequences. For instance, gut microbiota have a causal role in the development of obesity in mice. Ridaura et al.4 demonstrated that when gut microbiota from human twins who were discordant for obesity were transferred to germ-free mice, the mice receiving the microbiota from the obese twin had significantly more body mass and fat tissue than mice receiving the microbiota from the lean twin. The donor obese individuals had a higher ratio of certain phyla of bacteria (Firmicutes to Bacteroidetes)and overall reduced bacterial diversity in the gut compared with lean individuals.5
Currently, there is no scientific consensus as to what constitutes a “healthy gut microbiome,” but bacteria can be categorized as being either beneficial or potentially deleterious based on their metabolic activities and fermentation products. Bacteria having almost exclusively saccharolytic metabolism (breakdown of carbohydrate for energy) with little peptolytic metabolism (breakdown and metabolism of peptides) such as lactobacilli and bifidobactera are considered potentially beneficial.3Researchers are actively trying to discern what gut microbial metabolites or patterns of metabolites may be predictive of an optimal host-microbe-metabolism through advances in metabolomics and metagenomics.6 A recent study identified specific gut microbial metabolites, measured in plasma and urine, that were present in higher concentrations in patients with coronary heart disease (CHD) compared with healthy subjects, suggesting that a deranged gut microbiota composition (dysbiosis) is present in the CHD patients.7 There is a large and growing body of evidence indicating that gut dysbiosis may be central in contributing to metabolic, immune and cognitive dysfunction as well as cardiovascular disease and cancer.8-14
The composition of each individual’s gut microbiota is influenced by the environment, genetics and most importantly by diet, and remains relatively stable over time.15People possess a “core” microbiome which appears to reflect the metabolic pathways and systems used by the resident microbial population to generate energy from the host diet.5 Some researchers have demonstrated that the “core” microbiomes can be classified based on the characteristics of the predominant microbial genera.16,17Differences in habitual diets among groups within a given social group (e.g. urban America) can show large variations in plasma metabolomes (circulating metabolites largely produced by the gut microbiota) while differences in respective gut bacterial communities are relatively modest, indicating that the core gut microbiome can accommodate and efficiently metabolize substrates from a range of varied diets.18Core microbial profiles show major differences between populations with radically different diets and environments.19 That being said, the microbiome demonstrates a significant ability to adapt to sudden or significant changes in diet composition, such as switching from animal to a plant-based diet or vice versa by quickly altering the bacterial composition to meet the functional demands to metabolize alternative substrates.20-24
Plant-based diets tend to promote the growth of saccharolytic bacteria and plant fiber is the main source of carbohydrate for the colonic bacteria.3 A major end product of saccharolytic bacteria are short chain fatty acids (SCFAs) which are absorbed into the blood stream. Societies that consume a plant-rich diet exhibit a gut microbiome that is characterized by a higher Bacteroidetes to Firmicutes ratio,19 which is opposite to that seen in obese subjects in the U.S.5 Up to 90% of ingested plant polyphenols, such as soybean isoflavones, make their way to the colon where they can interact directly with the microbiota or can be used as bacterial substrates to produce SCFA and other metabolites.25
Soy and the Microbiota
Soy contains four major components which can impact the composition of the microbiota in a potentially prebiotic manner: fiber, oligosaccharides, isoflavones and protein. A brief summary of the evidence for plausible beneficial effects of these components is presented below.
No human studies have directly evaluated the effects of soy fiber (derived from the soybean cotyledon) on the gut microbiome, but benefits of it on some aspects of bowel function and metabolic health have been known for some time.26,27 Kapadia et al.28 evaluated the fermentation characteristics of soy fiber in vitro using human fecal bacteria. Compared with the control and oat fiber substrates, soy fiber produced significantly more SCFAs.28 A similar experiment using dog fecal bacteria showed that soy fiber was moderately fermentable and produced equivalent SCFAs to that of sugar beet fiber or pulp, citrus pectin and pea fiber.29
Kapadia et al.28 also evaluated soy oligosaccharides (carbohydrates made up of 3 to 9 monosaccharides) in human fecal bacterial cultures and found a 4.6-times increase in SCFAs compared with soy fiber, indicating that soy oligosaccharides have a much higher “prebiotic” potential on a weight basis. The major soybean oligosaccharides are raffinose and stachyose, which are not digested in the small intestine and enter the colon as substrates for the resident bacteria. Commercial preparations of soy oligosaccharides are available and presumably marketed for their prebiotic potential.30 Soy oligosaccharides appear to promote the growth of bifidobacteria, and not bacteria such as Clostridium difficile or E coli, since only the former specifically utilizes these oligosaccharides as substrates.3,31-33 Fermentation studies using human fecal bacteria mixtures have confirmed that soy oligosaccharides tend to promote the growth of bifidobacteria.30,34-36 Studies on people consuming either pure raffinose37 or soy oligosaccharide mixtures36,38-40 also show a bifidogenic property of soy oligosaccharides. Nevertheless, additional studies are needed to better understand the potential beneficial effects of soy oligosaccharides on the overall microbiota profile.
Studies to evaluate the effect of soy protein on gut microbial changes are challenged by the fact that the protein is associated with isoflavones, and possibly fiber and oligosaccharides, depending on the source of soy protein (isolate, concentrate or whole soy). Human studies are limited to analyses of fecal microbiota, which does not permit direct evaluation of the microbial populations resident in the gut. However, short-term41,42 and long-term43 studies of soy protein with isoflavones consumption in postmenopausal women have demonstrated consistent increases in fecal Bifidobacterium and other microbial differences that were unique to each study. All three studies noted that specific changes in microbial profiles showed significant correlations to the equol producing status of the subjects, which may be expected since the conversion of the isoflavone daidzein to equol is mediated by specific gut bacterial species.44 A 2 week study found the consumption of fermented, in comparison with non-fermented, soymilk (100 g/day) caused significant increases in fecal bifidobacteria and lactobacilli with reductions in clostridia.36 Unfermented soymilk produced similar findings but the results were not statistically significant. In addition, the presence of live bacteria in the fermented soymilk confounds the interpretation of this study.
Finally, Fernandez-Raudales et al.45 reported that obese adult men consuming a low glycinin (a fraction of soy protein) or conventional soymilk for 3 months had significantly lower fecal Firmicutes to Bacteroidetes ratios and lower fecal Bifidobacterium compared with bovine milk. It is not clear why this study reported a reduction in bifidobacteria with soy protein consumption and why all test products reduced bacterial diversity over 3 months.
A study of infants switched from cow’s milk formula to soy-based formula for one month showed that the diversity of bacteria and presence of beneficial bifidobacteria and ruminococci were similar to that seen with cow-milk formula,46 indicating that the microbiota of formula-fed infants may be similar regardless of protein source. More research applying sequence analyses of gut microbiota are needed in this area. Malawian infants aged 6 to 18 months, also did not show significant differences in their fecal microbial profiles (using sequencing methods) after receiving one of four interventions: Control, lipid-based nutrient supplements (cow milk or soy-based) or corn-soya blend.47 The lack of difference may be due to the high inherent gut bifidobacteria presence in this population, as well as dominance by other species such as Prevotella and Faecalibacterum.47
Animal studies may provide some advantages in helping to learn about the role of dietary protein on the gut microbiota. Responses of the microbiota in animals to changes in dietary protein appear to be similar to what is seen in humans. Lee et al.48demonstrated that when 20% of the casein in a cholesterol-enriched laboratory diet was substituted by soy protein from freeze-dried soymilk for 6 weeks, rats had an increased fecal Firmicutes to Bacteroidetes ratio compared to the cholesterol-enriched diet alone. An et al.49 found microbial diversity was significantly higher for rats fed soy protein for 16 days compared with casein, but not compared with a diet containing fish meal. In another recent study, Zhu et al.50 found distinctions in microbiota of Sprague-Dawley rats fed diets differing only in protein source for 90 days,. Analyses of the microbial sequences revealed that the meat-fed groups had more similar gut microbiota compared with the non-meat (casein and soy-fed) groups, with the meat protein groups having a higher Firmicutes to Bacteroidetes ratio compared with the non-meat group.50 Analyses of the feces revealed that the soy protein fed group had the highest content of SCFAs compared to all other groups.51
Another study found that in comparison with milk protein, soy protein increased the microbial diversity throughout the gut of hamsters.52 Increased microbial diversity in humans is associated with a “lean” phenotype5 and has been shown to be associated with metabolic health, while individuals with low richness have a relatively higher incidence of dyslipiemia, higher fat mass, insulin resistance, inflammation and frailty (elderly).53-55 In this hamster study, three differently processed soy proteins were evaluated and all soy proteins showed significant differences in microbial profiles compared to the milk protein and were most similar to each other.52 Importantly, microbial families present at significantly higher concentrations in the gut of soy protein-fed groups were correlated with lower blood lipid concentrations and the expression of hepatic genes that could account for the observed lipid concentrations. Conversely, those microbial families more abundant in the milk protein-fed groups correlated with higher plasma lipid concentrations and expression of hepatic genes that contribute to the higher lipid concentrations.52 This study provides evidence that soy protein may exert its cholesterol lowering activity in large part through its ability to modulate the gut microbiome.
Summary and Conclusions
The emerging data on the potential prebiotic properties of soy products indicate that consuming these products can help promote a healthy gut microbiota. The role of the diet in maintaining health is currently receiving more attention given that the diet is one of the most significant factors impacting the gut microbial profile. Future research on the gut microbiota and soy promises to provide more insights into how soy consumption contributes to maintaining overall health.
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