Soy and the Microbiota/Microbiome

The health effects of soy foods and various soybean components have been widely investigated, although with respect to the latter, most focus has been on protein and isoflavones. A wide range of outcomes has been examined including many chronic diseases in epidemiologic studies and many risk factors for or markers of chronic diseases in clinical studies. One outcome for which a better understanding is needed is the impact of soy on the microbiota/microbiome. Fortunately, several ongoing trials funded by Soy Nutrition Institute (SNI) Global, involving both children and adults, will help address this need.

Perhaps the most obvious way soy may impact the microbiome is via the consumption of fermented soy foods, such as tempeh, miso, and natto. Fermented soy products can contain microbes which may act as a probiotic if these microbes escape digestion in the upper gut. For example, an Indonesian study involving 10 healthy women found that after consuming 100g/d tempeh for 28 days, there was a significant increase in Bifidobacterium and Akkermansia muciniphila populations, changes which are viewed as potentially beneficial.¹ These results concur with a shorter-term study in humans² and animal research.^3,4 An important caveat is that if tempeh is cooked at a high temperature for a long time or pasteurized, the microbes inherent in this product will be killed; although this may not completely eliminate its impact on the microbiome.

Several studies have investigated the effects of both fermented and unfermented soymilk on the microbiota.^5-8 In one study involving healthy men, the relative abundance of Firmicutes significantly decreased whereas the relative abundance of Bacteroidetes increased in response to 500ml/d soymilk.⁷ Correspondingly, the Firmicutes to Bacteroidetes ratio decreased significantly. Again, these changes are viewed as desirable. However, there were no benefits observed in a study in which infants were fed soy-based infant formula for 1 month after first being fed cow’s milk formula.⁶ In a Taiwanese study, adults first consumed 250ml fermented or unfermented soymilk twice per day for 2 weeks and then switched to the opposite milk for another 2 weeks.⁵ The population of Lactobacillus increased in response to unfermented soymilk, but in response to fermented soymilk, the populations of both Bifidobacterium spp. and Lactobacillus spp. increased as did the ratio of Bifidobacterium spp. and Lactobacillus spp. to Clostridium perfringens. Thus, fermented soymilk outperformed unfermented soymilk. The superiority of fermented vs. unfermented soymilk concurs with the results of a Japanese study.⁸

In terms of soybean components, more than 30 years ago it was shown that soybean oligosaccharides can increase Bifidobacterium,^9,10 and for this reason, Japanese researchers suggested using a soybean oligosaccharide extract as a sugar substitute.¹⁰ More recent research in pigs supports the prebiotic effects of soybean oligosaccharides.¹¹  

It is not surprising that the impact of isoflavones on the microbiota has been studied given the general focus on isoflavones and the known role that the microbiota play in the metabolism of these diphenolic soybean constituents.¹² However, in a Spanish study, 1 month of isoflavone supplementation (80mg/d) increased the relative abundance of the genus Slackia,¹³ which has been associated with periodontal disease.¹⁴ Even soybean oil has been studied for its effect on the microbiota. For example, a study in mice that intervened with diets containing either olive oil, soybean oil, or coconut oil found that the first 2 oils increased microbial diversity relative to coconut oil.¹⁵

Finally, numerous studies on the microbiota provide insight into possible differences between plant and animal protein. In a small study involving 23 vegetarians and 23 omnivores, no major differences between dietary groups were observed in terms of fecal bacterial richness, alpha diversity, or beta diversity. However, a minority of potential pathobionts tended to be elevated in omnivores compared to vegetarians, whereas potential probiotic species tended to be higher in the vegetarians.¹⁶ In contrast, a cross-sectional analysis of 2 European cohorts found there was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity.¹⁷ 

More directly relevant to soy is a randomized, double-blind, parallel-design trial involving 38 overweight individuals who received a 3-week isocaloric supplementation with casein, soy protein, or maltodextrin as a control.¹⁸ The protein supplement was intended to provide 15% of total energy intake at the expense of starch, thus creating a high-protein diet. Although protein supplementation did not alter microbiota composition, it did induce a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Casein and soy protein differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death.

In summary, soy foods may potentially impact the microbiota/microbiome through multiple components and mechanisms, although at the present time, data are too limited to conclude that any potential changes account for the proposed impact of soy on clinically relevant outcomes. Ongoing research may provide insight as to whether this is the case. 

References

1. Stephanie, Kartawidjajaputra F, Silo W, Yogiara Y, Suwanto A. Tempeh consumption enhanced beneficial bacteria in the human gut. Food Res. 2019;3:57-63.
2. Stephanie, Rath NK, Soka S, Suswant A. Effect of tempeh supplementation on the profiles of human intestinal immune system and gut microbiota. Microbiology Indonesia. 11:11-7.
3. Soka S, Suwanto A, Sajuthi D, Rusmana I. Impact of tempeh supplementation on gut microbiota composition in Sprague-Dawley rats. Research J Microbiology. 2014;94:189-98.
4. Soka S, Suwanto A, Sajuthi D, Rusmana I. Impact of tempeh supplementation on mucosal immunoglobulin A in Sprague-Dawley rats. Food Sci Biotechnol. 2015;24:1481-6.
5. Cheng IC, Shang HF, Lin TF, et al. Effect of fermented soy milk on the intestinal bacterial ecosystem. World journal of gastroenterology. 2005;11:1225-7.
6. Piacentini G, Peroni D, Bessi E, Morelli L. Molecular characterization of intestinal microbiota in infants fed with soymilk. J Pediatr Gastroenterol Nutr. 2010;51:71-6. https://10.1097/MPG.0b013e3181dc8b02
7. Fernandez-Raudales D, Hoeflinger JL, Bringe NA, et al. Consumption of different soymilk formulations differentially affects the gut microbiomes of overweight and obese men. Gut Microbes. 2012;3:490-500. https://10.4161/gmic.21578
8. Inoguchi S, Ohashi Y, Narai-Kanayama A, et al. Effects of non-fermented and fermented soybean milk intake on faecal microbiota and faecal metabolites in humans. Int J Food Sci Nutr. 2012;63:402-10. https://10.3109/09637486.2011.630992
9. Hayakawa K, Mizutani J, Wada K, et al. Effects of soybean oligosaccharides on human faecal flora. Microbial Ecol Health Dis. 1990;3:292-303.
10. Hata Y, Yamamoto M, Nakajima K. Effects of soybean oligosaccharides on human digestive organs: estimate of fifty percent effective dose and maximum non-effective dose based on diarrhea. Journal of clinical biochemistry and nutrition. 1991;10:135-44.
11. Zhou XL, Kong XF, Lian GQ, et al. Dietary supplementation with soybean oligosaccharides increases short-chain fatty acids but decreases protein-derived catabolites in the intestinal luminal content of weaned Huanjiang mini-piglets. Nutr Res. 2014;34:780-8. https://10.1016/j.nutres.2014.08.008
12. Soukup ST, Engelbert AK, Watzl B, Bub A, Kulling SE. Microbial metabolism of the soy isoflavones daidzein and genistein in postmenopausal women: Human intervention study reveals new metabotypes. Nutrients. 2023;15. https://10.3390/nu15102352
13. Guadamuro L, Azcarate-Peril MA, Tojo R, Mayo B, Delgado S. Impact of dietary isoflavone supplementation on the fecal microbiota and its metabolites in postmenopausal women. Int J Environ Res Public Health. 2021;18. https://10.3390/ijerph18157939
14. Shen C, Simpson J, Clawson JB, Lam S, Kingsley K. Prevalence of oral pathogen Slackia exigua among clinical orthodontic and non-orthodontic saliva samples. Microorganisms. 2023;11. https://10.3390/microorganisms11040867
15. Lopez-Salazar V, Tapia MS, Tobon-Cornejo S, et al. Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil. The Journal of nutritional biochemistry. 2021;94:108751. https://10.1016/j.jnutbio.2021.108751
16. Wu YT, Shen SJ, Liao KF, Huang CY. Dietary plant and animal protein sources oppositely modulate fecal Bilophila and Lachnoclostridium in vegetarians and omnivores. Microbiol Spectr. 2022;10:e0204721. https://10.1128/spectrum.02047-21
17. Bel Lassen P, Attaye I, Adriouch S, et al. Protein intake, metabolic status and the gut microbiota in different ethnicities: Results from two independent cohorts. Nutrients. 2021;13. https://10.3390/nu13093159
18. Beaumont M, Portune KJ, Steuer N, et al. Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans. Am J Clin Nutr. 2017;106:1005-19. https://10.3945/ajcn.117.158816