Some phytochemical compounds that modulate gut microbiota.
Currently, herbs, medicinal spices, green medicine, or traditional Chinese medicine has gained many followers in the world, especially as a way of life and as an alternative to the indiscriminate use of synthetic medicines such as antibiotics. These natural products are rich in secondary metabolites or phytochemicals, which are chemical compounds of relatively complex structures and restricted distribution; these compounds have defensive functions against insects, bacteria, fungi, parasites, and viruses. Likewise, several studies have shown their effectiveness in the prevention and treatment of several diseases such as cancer, autoimmune diseases, gastrointestinal diseases, diabetes, neurodegenerative diseases, Crohn’s disease, and human immunodeficiency virus (HIV), among others. In addition, this review addresses the mechanisms of action of the herbs and medicinal spices on intestinal microbiota, increasing competitive exclusion in the intestinal membrane and inhibiting bacterial translocation and damage to the intestinal barrier.
- gut microbiota
- phytochemical compound
Through history, the individual and collective experiences of a population have been systematized and transformed as part of their popular culture, their means of action, and their wisdom. Popular customs based on empirical bases have found justification with the development of science and technology, after having been used for a long time. In this sense, due to advances in the areas of knowledge, especially medicine, genetics, immunology, and molecular biology, it is obvious to seek explanations and incontestable facts that justify the use of some popular practices that may be useful in the treatment of different health problems. These practices are phytochemical compounds, which have been the subject of deep research around the world .
The phytochemicals have been used for over 60,000 years to prevent or cure diseases that affect humans . It is estimated that about 260,000 species of plants are known today, of which 10% can be considered as medicinal, with many phytochemical properties. According to the classification of medical treatments of phytotherapy, in modern and past times, many regions are favored by the proportion of phytochemical compounds, which can vary appreciably to the established percentage, since the totality of the vegetal flora is not known .
Despite the agro-industrial development of humanity and the strong influence of the large pharmaceutical industries, phytochemical compounds are the first sources for medical treatment in many countries, due to its effectiveness against different pathologies, low production cost, and slight residual effect [4, 5, 6]. Its use is strengthened and expanded more and more, appearing in new and novel active principles, both for human and veterinary use. It is estimated that between 75 and 80% of the world population used phytochemical compounds one way or another, China and India being the countries that used the natural products of plant origin the most, as part of their cultural roots. These beneficial phytobiotics are used mainly as food or part of the food, although they are also used as pharmaceutical preparations. In these countries, traditional medicine is used daily as a lifestyle to prevent, cure, and/or alleviate diseases. In this sense, natural compounds have been used to treat diseases that damage the nervous, cardiovascular, respiratory, gastrointestinal, renal, metabolic, immune, and musculoskeletal systems, besides preventing or curing metabolic disorders of the main biomolecules of the organism [7, 8].
Plants are natural laboratories where a large amount of chemical substances are biosynthesized, and in fact, they are considered the most important source of chemical compounds that exists. A large percentage of the active ingredients included are called “phytochemical compounds or secondary metabolites,” which are chemical compounds of relatively complex structures and restricted distribution; among these metabolites, those with defensive functions against insects, bacteria, and fungi, among others, as alkaloids, non-protein amino acids, steroids, phenols, flavonoids, glycosides, coumarins, quinones, tannins, and terpenoids, are common. There is great variation in the concentration of these phytochemicals in the plant, and there is no maximum production pattern nor special storage organs; however, it is common that the highest concentrations of these types of compounds are in flowers, leaves, and seeds [9, 10].
Currently, research on natural products is focused on the discovery of new active ingredients with beneficial properties against several systemic and infectious diseases in humans and animals . It has been proven that synthetic substances sometimes have more harmful side effects than the diseases they treat; some synthetic antioxidant compounds cause toxic and mutagenic effects . Thus, several authors indicate the need to reuse natural preparations as alternatives to the indiscriminate use of antibiotics and their microbial resistance [13, 14]. However, it is currently unclear how phytochemical compounds have a high compatibility with the human organism , because these have no enzymatic affinity and are poorly absorbed by the intestinal lumen.
Intestinal microbiota plays an important role in maintaining intestinal integrity and function; a loss in microbial balance causes severe damage at the local and systemic level [15, 16, 17]. It is important to note that the microbiota in the first years of life of children is unstable, dominated mainly by
Many investigations have focused on demonstrating the antimicrobial effect of phytochemical compounds; however, there are contradictions in the mechanism of action of the active principles. These phytochemicals compounds could have bacteriostatic or bactericidal action as well as inhibit the adhesion of pathogenic bacteria to the intestinal and urinary mucosa. Every day the use of phytochemicals to reduce the pathogenic effect of intestinal bacteria is more frequent, due to the increase of antimicrobial resistance to antibiotics [23, 24]. Therefore, the aim of this review is to summarize the role of herbs and medicinal spices like modulators of gut microbiota.
2. What are the phytochemical compounds?
Phytochemicals are chemical compounds synthesized by plants that fulfill nonessential functions, so that their absence is not fatal for it, since they do not intervene in the primary metabolism. These compounds intervene in the ecological interactions between the plant and its environment . They also differ from the primary metabolites in that each of them has a restricted distribution in the plant kingdom, sometimes to only one species or a group of them, so many of them are useful in
The study of these substances was initiated by organic chemists of the nineteenth century and the beginning of the twentieth century, who were interested in these substances due to their importance as medicinal drugs, poisons, flavorings, glues, oils, waxes, and other materials used in the industry . In fact, the study of phytochemicals stimulated the development of separation techniques, spectroscopy to elucidate their structure, and synthesis methodologies that today contribute to the development of contemporary organic chemistry .
In addition, the content of the active principles of a plant can vary significantly due to differences from one locality to another and, even within the same locality due to several agrochemical properties of the land, the season and variations for temperature, precipitation, pollution, lunar cycle, or other factors . The plants have characteristics that allow them to influence through their components not only by direct contact but also remotely by means of emanations. There are plants that through the emanations of their active ingredients can eliminate the spores of fungi, protozoa, and malignant bacteria [2, 10]. The recognition of biological properties of many phytochemical compounds has encouraged the development of this field, for example, in the search for new drugs, antibiotics, insecticides, and herbicides. Moreover, the growing appreciation of the highly diverse biological effects of these compounds has led to the reevaluation of the different roles they have in plants, especially in the context of ecological interactions .
Phytochemicals can be divided into three large groups, based on their biosynthetic origins: phenolic compounds, terpenoids, and nitrogen compounds or alkaloids. They can also be divided according to their biosynthetic pathway and chemical structure: terpenoids, alkaloids, betalains, glucosinolates, cyanogenic glycosides, polyacetylenes, anthocyanins, and other flavonoids .
Currently, many synthetic drugs produced by the pharmaceutical industry have very harmful side effects and are not effective in alleviating or reducing the symptoms of many diseases such as cancer, HIV, Alzheimer’s, and other chronic diseases. Therefore, modern medicines where phytochemicals are included as an alternative source may meet the therapeutic requirements of patients. In this sense, there is high availability of these natural products from plant sources that act as potent curative medicines . Phytochemicals including polyphenols, flavonoids, and others have the potential to provide a defense against oxidative damage. Plant extracts and phytoconstituents are found to be effective as radical scavengers and inhibitors of lipid peroxidation [30, 31]. A wide range of antioxidants from both natural and synthetic origin to treat various human diseases has been proposed .
Other metabolites have wide medicinal properties, such as sterols used as part of hormones and vitamins; triterpenes have anthelminthic, antiseptic, expectorant, antibacterial, and diuretic activity. Simple phenols have antifungal activity. The tannins (condensed tannins) have astringent, antiseptic, antibacterial, and antifungal properties. The coumarins are used in medicine for their anticoagulant and antibacterial action. The flavonoid glycosides (anthocyanins and quercetins) are attributed effects on the blood supply of the bronchi and bronchodilation. Quinones (specifically naphthoquinones) are characterized by their antibacterial and antifungal action. Cardiotonic glycosides stimulate cardiac function. The alkaloids stimulate the central nervous system and have an anesthetic effect. Saponins are precursors of steroidal hormones and corticosteroids and have emulsifying and hemolyzing functions [4, 5, 6, 33].
3. Role of the phytochemical compounds to modulate gut microbiota
The gut microbiota begins to mature from the second year of life and has various roles such as nutrient absorption and food fermentation , proper modulation of the immune system to the gastrointestinal tract (GIT) of the host , and the physiological mechanisms against pathogens . In adults, the most prevalent phyla representatives are
The bacterial population of the
Many bacterial species are commensal flora in the intestine, and others are highly pathogenic such as
|Phytochemical compounds||Sources||Part used||Model experiment||Outcomes||References|
|Phenolic acids, stilbenoids, flavonols, dihydroflavonols, and anthocyanins||Fruits||Humans||↑|||
|Chlorogenic acid-polyphenols||Green coffee||Bean||High fat-fed mice||↑|
|Phenolic compounds||Whole plant||In vitro||↓|||
|[47, 48, 49, 53]|
|Anthocyanidins and flavonoids||Fruits||Mice and high fat-fed mice||↑|
|[21, 22, 54, 55, 56]|
|Anthocyanidins||Fruits||In vitro||↓||[57, 58, 59]|
|Anthocyanidins||Flowers||High fat-fed mice||↑||[22, 25]|
|Syringe, p-coumaric, 4-hydroxybenzoic, and vanillic||Needles||Mice||↑|||
|Catechins, flavan-3-ols, and monomeric flavan-3-olrich rich||Green tea||Leaves||Humans||↓|
|[59, 61, 62]|
|Procyanidins, catechin and epicatechin||Fruits||Mice||↑|||
|Gallic acids||Leaves||Mice||↓||[64, 65]|
|6′,7′-dihydroxy-bergamottin, officinalin, stenocarpin isobutyrate, officinalin isobutyrate, 8-methoxypeucedanin, and peucedanin||Fruits||In vitro||↓|
|Coumarin-1,2,3-triazole conjugate and 3-heteroarylazo 4-hydroxy||In vitro||↓||[49, 68, 69]|
|Terpineol||Whole plant||In vitro||↓|||
|Petalostemumol||Flowers||In vitro||↓||[47, 70]|
|1α, 3β, 23-trihydroxyolean-12-in-29-oic acid||Cortex||In vitro||↓|||
|23-hydroxyursolic acid, hederagenin, 3-O-α-L-arabinopyranosyl-echinocystic acid, 3-O-α-L-arabinopyranosyl-oleanolic acid, and 3-O-α-L-arabinopyranosyl-ursolic acid||Stem bark||In vitro||↓|||
|4-methoxy-1-methyl-quinolin-2- (1H) -one||Leaves||In vitro||↓|
|Sanguinarine, chelerythrine, protopine and allocryptopine and phenolics, gallic, protocatechuic, p-hydroxybenzoic, m-hydroxybenzoic, gentisic, p-coumaric, caffeic, ferulic, and sinapic acids||Roots and leaves||In vitro||↓||[73, 74]|
|Sanguinarine and dihydrosanguinarine||Seeds and leaves||In vitro||↓|||
Currently, many investigations focus on the search for therapeutic treatments through diet to modulate the intestinal microbiota, reducing inflammation in this organ, preventing chronic and degenerative diseases . It has been shown that small concentrations of active ingredients from medicinal plants or other plant sources have microbiostatic and microbicidal activities against enteric pathogenic microbiota . An increase of the competitive exclusion in the intestinal epithelium guarantees a greater metabolization of the phytochemical compounds by the bacteria and therefore benefits the biological response of the host [54, 77]. Although the mechanisms are not well, the phytochemical compounds can reduce the proliferation of pathogenic bacteria in the GIT, affect cell reproduction, mediate microbial metabolic processes, and regulate signal translation or genetic expression with phospholipoidal cell membranes, thus increasing the permeability and loss of cellular constituents, imbalance of the enzymes to the production of cellular energy and synthesis of organelle compounds, and destruction or inactivation of genetic material [45, 46, 47, 48, 78].
3.1 Phenolic compounds
Scientific evidences show that within the phytochemical compounds, polyphenols are the most effective antimicrobials. In this sense, the phenolic compounds such as flavonols, flavones, and flavanones, and phenolic acids are poorly metabolizable by some gut microbiota. However, species such as
The relationship between the most representative phylum of the intestine,
Several authors have reported the modulating effect of anthocyanidins on the colonic microbiota and some inflammatory markers [21, 22, 60]. Anthocyanidins have the ability to inhibit the growth of intestinal pathogenic bacteria; apparently an interaction exists between the phenolic compounds and the local microbiota specifically (mainly
Green tea has high concentrations of catechins, which belong to the group of flavonoids; these secondary metabolites have good effects against
As an interesting fact, the increase of the
According to the in vitro results, the family of coumarins and reducing carbohydrates abundant in the hexane, chloroform, and ethyl acetate extracts of the leaves of
On the other hand, phytochemical compounds such as terpineol from
Other groups of phytochemicals with bactericidal or bacteriostatic importance are alkaloids. In an investigation, 4-methoxy-1-methyl-quinolin-2- (1H)—one obtained from three tropical plants such as
In general, the antimicrobial activities of several phytochemical compounds based on chemical studies, in vitro and in vivo, are known. However, due to the alimentary habit of a part of the world population, many of these medicinal compounds are not used, mainly as part of the diet, as aqueous extracts, or as alcoholic extracts, although other times they are used empirically, showing their beneficial effect. The daily use of phytochemicals in a controlled manner and according to scientific bases, both chemical and biological, could prevent or treat many ailments and diseases related to intestinal dysbiosis in humans.
This review has highlighted the role of the phytochemical compounds like modulators of gut microbiota. It was identified that alkaloids, steroids, phenols, flavonoids, glycosides, coumarins, quinones, tannins, and terpenoids are the main phytochemical compounds with biological activity. In addition, in vitro and in vivo experiments demonstrated that these beneficial chemical compounds can reduce the proliferation of pathogenic bacteria in the gastrointestinal tract through various biochemical and physiological processes that cause disturbances in the bacterial cell membrane, which causes competitive exclusion in the epithelial membrane by a greater expression of
Conflict of interest
The authors declare no conflict of interest.