Ingredient focus on
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Prebiotics: to take or not to take? That is the question!
KEYWORDS
Microbiota
Prebiotics
Gut
Soil
Herbal medicine
Polyphenols
Immune health
Immune health
Before we start reading, I invite you to look out your window. What do you see? A variety of brown and gray buildings surrounded by cement and asphalt or an explosion of plants, soil, grass, flowers, butterflies, trees, insects, bees, and birds?
Now, think back about your meals over the past four weeks. Were your plates filled with vibrant colors from vegetables, grains, and cereals, or dominated by pale tones from meat and low-fiber carbohydrates like processed flour bread, polished grains, and chips?
You might wonder how this relates to prebiotics. In fact, there is a strong connection.
Why gummies?
Today, chronic non-communicable diseases (NCDs) such as diabetes, obesity, cardiovascular diseases, depression, anxiety, cancer, autoimmune diseases, and inflammatory diseases are closely linked to our lifestyle. Our modern, tech-heavy, highly hygienic world (where we are told to use antiseptics on every surface of our bodies and environments) leads us to live in “bubbles” — our cars, the house without a yard, the office with closed windows and air conditioning. We are moving further away from our kitchens and closer to food delivery apps and frozen foods from the supermarket. We have lost the pleasure of preparing our own meals with fresh, locally-produced ingredients that respect seasonal variations.
I live in Brazil and was born and raised in the Midwest. I like to think about how my grandparents, farmers in the 1950s, understood the relationship between planting and health. Their rural lifestyle was crucial for the health of my family's - first (my mother) and second (me) generations. But the third generation (my son) is already facing problems!
When I hear my mother and aunts talking about eating only fruits and vegetables, consuming meat in moderation, playing barefoot, and swimming in the river in front of their house, I see the explosion of microscopic life diversity - the microbiota, and the variety of fibers (pumpkins with their leaves and flowers), resistant starches (found in manioc and sweet potato), grains and cereals grown for personal consumption, and the secondary metabolites (like polyphenols) present in cerrado fruits (such as pequi (Caryocar brasiliense camb) and bocaiúva (Acrocomia aculeata (Jacq.) Lodd. ex Mart).
Here is another critical definition to show how prebiotics - specific residues or culprits - are involved in protecting against NCDs in my family's first and second generations (perhaps yours too!). I like to think of prebiotics as “green manure for the microbiota.” Green manure brings life to the soil, renewing the organic mass of bacteria and fungi, making nutrients available, and forming more soil. Similarly, prebiotics in their natural environment - whether in the soil or the large intestine - stimulate the growth of commensal probiotic microbiota, generating a world of metabolites, (microbial metabolome derived from the activity of CAZyme and PAZyme enzymes).
In this symbiosis between commensal probiotic bacteria and prebiotics participate in the production of:
- Protein metabolism;
- Antimicrobial metabolites (such as bacteriocins);
- Metabolites such as short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate;
- The endless metabolites from the breakdown of the C ring of flavonoids;
- The available carbons derived from the various carbon groups of polyphenols and the carbon polymers of resistant starches and insoluble fibers;
- Production of vitamins;
- Enteric neurotransmitters;
- Increase in abundance and diversity of probiotic microbiota are some of the results.
These metabolites reach different receptors. Mainly, G protein-coupled estrogen receptor (GPR) type receptors, spread throughout the other organs of the human body, resulting in anti-inflammatory, metabolic, endocrine, and immunological effects that can prevent or treat various diseases.
It’s interesting to think that today I live in a very different environment from my grandparents, with buildings and “bubbles” as I mentioned. Although I have access to soil and manage medicinal plants, providing direct contact with the microbiota and soil fauna (this is therapeutic and stimulating for the immune system, topics for other discussions), my food comes from the supermarket, not my own cultivation. However, I cook my meals.
Cooking is an act of self-care. You choose what and how much to use in preparing the “specific residues/prebiotics” for your microbiota. You can cultivate your microbiota.

No sugar-coating it
Next steps for candyceuticals
This environment was essential for building and cultivating the over 100 trillion bacteria that formed my family’s microbiota, helping us avoid obesity, diabetes, and chronic inflammatory diseases, at least from the second generation on. I can “blame” the prebiotics and polyphenols in fresh seasonal foods for “cultivating” my family's microbiota and the soil health. Respecting the seasonality of plants also respects soil health, preventing degradation from insecticides and chemical additives that mimic certain times of the year. Plant residues (peels, leaves, and stems- rich in prebiotics like lignans and non-flavonoid polymers) that were not consumed returned to the soil to become compost, feeding the diversity of soil fauna. For example, microbiota, fungi, viruses, mesofauna (e.g., mites, springtails), and microfauna (e.g., protozoa, nematodes).
Prebiotics are known as “a substrate – like carbon - that is selectively utilized by host microorganisms, conferring a health benefit.” Prebiotics were believed to be just “indigestible fibers for humans,” mainly digested by bifidobacteria and lactobacilli, commonly used as probiotics. Today, the concept of prebiotics extends to polyphenols — a class of secondary metabolites known in nature for giving color and flavor to flowers and fruits and in science as powerful antioxidants, anti-inflammatories, and antimicrobials (1).
Polyphenols derive from two primary metabolic pathways. The shikimic acid and the malonic acid pathways, which require carbon for their generation. This carbon comes from the degradation or metabolism of organic material (remember the prebiotics) in the soil. One of the actions seen in the metabolism of polyphenols is the generation of carbon for the microbiota to produce metabolites (I like the term postbiotics) that result in the beneficial effects of consuming these extracts on the body and soil. Polyphenols can promote the growth of common bacteria like Akkermansia muciniphila, Bacteroides thetaiotaomicron, and Faecalibacterium prausnitzii (2).
When we study the metabolic functions of bacteria in the microbiota, we find that they have 40 times more potent genetic machinery than humans. Among the many tasks of bacteria is the ability to metabolize “specific residues” – such as prebiotics, to produce postbiotics. I want to highlight two critical group of enzymes involved in the metabolism of these residues that reach the colon: PAZymes (polyphenol-associated enzymes) specifically involved in the metabolism of polyphenols found in bacteria (Adlercreutzia equolifaciens, Lactobacillus acidophilus, and Lactobacillus plantarum), and CAZymes (carbohydrate-active enzymes) found in bacteria of the genera Bacteroides spp and Prevotella spp., which can degrade complex carbohydrates (2).
Although food signifies prebiotics (sometimes suggesting prebiotics as treatment), I like to think of a “modern way of cultivating” the microbiota for systemic benefits. Through supplementation or complementing with prebiotics and polyphenols in various pharmaceutical forms—powders, shakes, capsules, sachets, tablets it is possible to associate a diversity of colors to my patients’ plates.
Supplementation with prebiotics and polyphenols in various pharmaceutical forms can complement the diet. My team and I have been working on preclinical (3, 4, 5, 6) and clinical (7, 8, 9, 10) supplementation studies in chronic diseases. Recently, we have published a study in Scientific Reports (10) that showed how a nutraceutical blend (prebiotics, minerals, and silymarin) positively modulated the gut microbiota in overweight Brazilian volunteers without changes to their diet or exercise routine. The study observed an increase in the Bacteroidetes phylum, Bacteroides, and Prevotella genera, (associated with a "rural lifestyle”). Additionally, the participants experienced improved sleep patterns, enhanced quality of life, changes in cytokine expression, and improvements in anthropometric parameters linked to cardiometabolic and inflammatory markers.
So, I do want to invite you to reflect on how you are cultivating your microbiota, and hope new colors will appear on your plate and, in consequence, in your life.


References and notes
- https://isappscience.org/for-scientists/resources/prebiotics/
- Rodríguez-Daza MC, Pulido-Mateos EC, Lupien-Meilleur J, Guyonnet D, Desjardins Y, Roy D. Polyphenol-Mediated Gut Microbiota Modulation: toward prebiotics and further. Frontiers in Nutrition. 2021 Jun 28;8. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.689456
- Pessoa AFM, Florim JC, Rodrigues HG, Andrade‐Oliveira V, Teixeira SA, Vitzel KF, et al. Oral administration of antioxidants improves skin wound healing in diabetic mice. Wound Repair and Regeneration. 2016 Oct 12;24(6):981–93. https://pubmed.ncbi.nlm.nih.gov/27684945/
- Nehmi VA, Murata GM, De Moraes RCM, Lima GCA, De Miranda DA, Radloff K, et al. A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice. Journal of Integrative Medicine/Journal of Integrative Medicine. 2021 Sep 1;19(5):439–50. https://pubmed.ncbi.nlm.nih.gov/34108131/
- Nehmi-Filho V, De Freitas JA, Franco LAM, Da Silva Fonseca JV, Martins RCR, Santamarina AB, et al. Novel Nutraceutical (silymarin, yeast β-glucan, prebiotics, and minerals) shifts gut microbiota and restores large intestine histology of diet-induced metabolic syndrome mice. Journal of Functional Foods. 2023 Aug 1;107:105671. https://www.sciencedirect.com/science/article/pii/S1756464623002712
- Santamarina AB, Jamar G, Mennitti LV, De Rosso VV, Cesar HC, Oyama LM, et al. The Use of Juçara (Euterpe edulis Mart.) Supplementation for Suppression of NF-κB Pathway in the Hypothalamus after High-Fat Diet in Wistar Rats. Molecules. 2018 Jul 21;23(7):1814. https://www.mdpi.com/1420-3049/23/7/1814
- Santamarina AB, Jamar G, Mennitti LV, De Cássia Cesar H, Vasconcelos JR, Oyama LM, et al. Obesity-related inflammatory modulation by juçara berry (Euterpe edulis Mart.) supplementation in Brazilian adults: a double-blind randomized controlled trial. European Journal of Nutrition. 2019 Jun 13;59(4):1693–705. https://link.springer.com/article/10.1007/s00394-019-02024-2
- Nehmi-Filho V, De Freitas JA, Franco LAM, Da Silva Fonseca JV, Martins RCR, Santamarina AB, et al. Novel Nutraceutical (silymarin, yeast β-glucan, prebiotics, and minerals) shifts gut microbiota and restores large intestine histology of diet-induced metabolic syndrome mice. Journal of Functional Foods. 2023 Aug 1;107:105671. https://www.sciencedirect.com/science/article/pii/S1756464623002712
- Nehmi‐Filho V, De Freitas JA, Franco LA, Martins RC, Turri JAO, Santamarina AB, et al. Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double‐blind clinical trial. Food Science & Nutrition. 2024 Jan 19;12(4):2436–54. https://pubmed.ncbi.nlm.nih.gov/38628220/
- Santamarina AB, De Freitas JA, Franco LAM, Nehmi-Filho V, Fonseca JV, Martins RC, et al. Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial. Scientific Reports. 2024 May 15;14(1). https://www.nature.com/articles/s41598-024-61909-3