Relevance of Indian Traditional Herbal Brews for Gut Microbiota Balance

Abstract

The considerable changes in lifestyle patterns primarily affect the human gut microbiota and result in obesity, diabetes, dyslipidemia, renal complications, etc. though there are few traditional safeguards such as herbal brews to maintain the ecological stability under intestinal dysbiosis. The present article is designed to collect all the scientific facts in a place to decipher the role of the Indian traditional herbal brews used to balance gut health for centuries. Computerized databases, commercial search engines, research papers, articles, and books were used to search by using different keywords to select the most appropriate published articles from 2000 onward to September 2023. A total of 1907 articles were scrutinized, 46 articles were finally selected from the 254 screened, and targeted information was compiled. Interaction of herbal brews to the gut microflora and resulting metabolites act as prebiotics due to antimicrobial, anti-inflammatory, and antioxidant properties, and modulate the pH of the gut. The effect of brews on gut microbiota has a drastic impact on various gut-related diseases and has gained popularity as an alternative to antibiotics against bacteria, fungi, viruses, parasites, and boosting the immune system and strengthening the intestinal barrier. Berberine, kaempferol, piperine, and quercetin have been found in more than one brew discussed in the present article. Practically, these brews balance the gut microbiota, prevent chronic and degenerative diseases, and reduce organ inflammation, though, there is a knowledge gap on the molecular mechanism to explain their efficacy. Indian traditional herbal brews used to reboot and heal the gut microbiota since centuries-old practice with successful history without toxicity. The systematic consumption of these brews under specific dietary prescriptions has a hope of arrays for a healthy human gut microbiome in the present hasty lifestyle with overall health and well-being.

Graphical Abstract

Introduction

Dietary food components influence the gut microbiota [1] as affect the composition and activity of about 10¹⁴ microorganisms that reside in the gut [2, 3]. A balanced gut microbiota is an indication of a healthy intestine and proper control of the changeover of endotoxin in the circulatory system [4]. Unaltered eating habits result in several gut health disorders including inflammatory bowel disease and obesity [5, 6]. Diseases such as type 2 diabetes mellitus, dyslipidemia, autism, Alzheimer’s, Parkinson’s, etc. are closely linked to the health of the intestinal microbiota [7]. Changes in dietary macronutrients can predominantly and invariably alter the gut microbiome within a single day [8]. Additionally, the high-fat diets have caused increased enteric DCA (deoxycholic concentrations), a bile acid, which promotes liver cancer [9] and induces the growth of Bilophalia wadsworthia, a sulfite-reducing bacterium that produces H₂S with animated intestinal tissue [10]. Devkota et al. have revealed that an animal-based diet including milk-associated saturated fats increases fecal bile acid concentrations and promotes B. wadsworthia growth in humans resulting in changes to the gut microbiota and the development of inflammatory bowel disease [10]. David et al. have reported that switching in the diet has resulted in changes in the microbiota makeup of the animal gut that can be monitored with feces [11]. The feces of persons using an animal-based diet have been reported reduced to Ruminococcus bromii, Eubacterium while an increased population of Bacteroides, Bilophila, Alistipes, rectale, Roseburia, Klebsiella, Shigella, Enterobacteriaceae, and Escherichia [11, 12].

Further, plant-based proteins including whey protein have been deciphered to enhance Lactobacillus and Bifidobacterium, though whey protein reduces the infectious Clostridium perfringens and Bacteroides fragilis [13]. Pea protein has been identified to increase the short-chain fatty acids (SCFAs) in the intestine. SCFAs are an anti-inflammatory product and have a potent role in keeping up the mucosal barrier [14]. Fat from animal sources including saturated fats has been reported to change the gut microbiota due to higher trimethylamine-n-oxide (TMAO), lipopolysaccharide (LPS), and reduced SCFAs [15].

The increased absorption of LPS due to increased intestinal permeability leads to reduced production of claudin, occluding, and zonula occludens-1 (ZO-1), the proteins responsible for the intestinal barrier, resulting in weak intestinal fencing to check the changeover of LPS, which induces the insulin resistance and inflammation [16]. Further, a high fat induces the circulation of cytokines through the Toll-like receptor 4 (TLR4) signaling route resulting in enhanced necrosis factors in the colon [17]. Frequent dysbiosis (e.g., raised bile acid, secondary ammonia, choline, and hydrogen sulfide) has been reported in high-fatty food lovers such as animal fat, and red and processed meat [18]. Kopf et al. have reported a significant decline in LPS in experimental groups consuming vegetables, whole grains, and fruits resulting in reduced inflammation compared to the control group [19]. Humans mainly have Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia with sparse populations of Spirochaetes, Cyanobacteria, Fusobacteria, and Saccharibacteria [20]. De Filippo et al. have depicted that feeding a vegetarian diet rich in polysaccharides, starch, and fibres to children enhances the number of Bacteroidetes, Firmicutes, Prevotella, and Xylanibacter, resulting in immunity bestower against inflammatory diseases compared to feeding a carbohydrate-rich European diet [21]. Pagliai et al. have reported that three months of diet intervention can significantly change the individual gut microbiome in humans [22].

Human gut bacteria have a vital role in the process of digestion, metabolism, body immunity, energy homeostasis, synthesis of vitamins, etc., and provide a balanced microbiome for maintaining good health and body immunity [23]. An invasion of the balanced microbiome by the overgrowth of one or more microbial colonies influences the body’s immunity resulting in many gastrointestinal diseases including irritable bowel syndrome (IBD), and inflammatory bowel disorder (IBS) [24]. Exposure to antibiotics in childhood and changes in the microbiome [25] are frequently associated with conditions such as childhood obesity, cardiovascular disease, atopy, asthma, neurological disorders, etc. [23]. Food is a most significant contributor and factor to the human gut microbiota, and a properly outlined diet regime can maintain it [26]. Ayurveda, the oldest Indian traditional healing system has the highest priority on promoting positive health rather than curing, and more than 1000 ayurvedic ahar (wholesome diet) are prepared and prescribed for the mutualistic value in the Indian gastronomy in different geographical zones of the country [27]. Tamang has revealed the use of these ancient Indian diets (either fermented beverages or fermented foods) since the Vedic period (1500–1000 BCE) to attain and sustain good physique, including the best gut health [27]. Additionally, there are certain herbal brews (either decoctions or infusions) that have been used to protect or cure gut-related disorders, otherwise impacting the renal, neurological, respiratory, circulatory, musculoskeletal, and immunological systems [28]. These herbal brews are also used as a source of instant energy and to quench thirst [29]. The sole objective of the present article is to develop a pharmacologically plausible discussion between gut microbial dynamics, and Indian traditional herbal brew-based gut therapies.

Materials and Methods

We performed an extensive literature search using computerized database of scientific (e.g., AYUSH research portal, PubMed, ScienceDirect, ResearchGate, Scholar, Google Scholar, and WHO ICTRP), and commercial (Google, Patent Scope, and Google patent) uses to obtain the maximum published articles like patents and their commercial applications, research papers, review articles, and books from different sources. The search was carried out using different keywords (e.g., Indian traditional herbal brews, herbal decoction, herbal infusion, Indian tisane, Ayurvedic infusion/-decoction, folk, and traditional uses, phytochemistry, pharmacology, reviews, etc.) to ensure maximum availability of the targeted information. The search results were limited to the year 2000 to September 2023 to ascertain the availability of the latest data with cross references. The abstract, keywords, and title of the retrieved articles were again screened to avoid multiplicity. A total of 1907 articles were scrutinized, and 46 articles were finally selected from the 254 screened. The selection criteria of an article during the screening were focused on their relevance, clarity, research gap, theoretical framework, biological studies, methodological relevance, literature review quality, etc. The exclusion of articles was based on replication, preference for research articles over reviews, limited description of active ingredients (lack of structure elucidation, chromatographic and spectral fingerprints), and poorly planned in-vivo or in-vitro studies. The targeted information from the finally selected articles was compiled as the present article.

Results and Discussion:

Herbals are a primary medicinal supplement for the ancient period to treat infections [30, 31]. The different extracts of herbs in different solvents including aqueous brews have diverse molecules, and many of these have antimicrobial, and radical scavenging characteristics and can protect the human body against cellular redox stress and pathogens with low toxicity [32]. Herbal brews are traditionally used for better health and have anti-inflammatory, antioxidant, anti-viral, anti-bacterial, and protective properties to the heart, liver, kidney, gastrointestinal system, etc. Therapeutic ingredients of these brews (Fig. 1) interact with the microbiome present in different parts of the body through the vagus nerve by means of different chemical messengers, such as hormones, peptides, and neurotransmitters [23]. As soon as brew passes through the oesophagus region, interacts with about 10¹⁴ microorganisms in the gut [2]. A few gut microbes can turn on immune cells in the gut wall resulting in the release of proinflammatory cytokines which influence the permeability of the blood–brain barrier [23]. An imbalanced microbiome causes psycho-biotic problems which are currently cured by means of changes in diet, and use of prebiotics, probiotics, antibiotics, and faecal microbiome transplantation (FMT) [33], and more recently, personalized nutrition advice-based therapy depending on microbiome data and other body ailments is on the rise [23].

Fig. 1.

Structure of the A kaempferol, B quercetin from A. vasica, P. guajava, T. arjuna, T. chebula, and T. foenum-graecum; C berberine from B. aristate, and T. cordifolia; D piperine from P. longum, and P. nigrum

Globally, about 60% of the population is using herbal medicine for different body ailments [34]. In India, there are currently about 2,50,000 registered traditional medical practitioners compared to about 7,00,000 in modern medicine, and traditional practitioners use about 7,500 plant species for curing different diseases out of recorded 20,000 plant species [34]. Ayurveda evolved in India between 2500 and 500 BC [35] based on the postulates of positive health (i.e., metabolically well-balanced human beings), and to rejuvenate the body through nutrition and diet [34]. Indian traditional health practitioners emphasize that every person has unique psychophysiological body chemistry, which is affected by lifestyle, diet, art adopted for stress management, digestion, and environmental factors [23].

The World Health Organization (WHO) deciphers the complete preparation of an active ingredient of traditional herbal medicines if adequate analytical methods are not available, otherwise, the standardized preparation of active ingredients should be allowed to define these ingredients [36]. Indian traditional therapies use several herbal brews (Table 1) as medicine for maintaining and creating an equilibrium in the physiology, and to cure specific disorders including the gut microbiome including yogurt and multi-herbal formulations (e.g., Ashwagandhadi Lehya, Chyawanprash, Triphala, etc.) [34]. Molecular investigations have revealed that these herbals have several inherent therapeutic features such as anti-inflammatory, hypoglycemic, immunomodulatory, antimutagenic, antibacterial, antineoplastic, adaptogenic, antioxidant, radioprotective, and chemoprotective, and promote the development of beneficial Lactobacillus and Bifidobacteria along the reduction of the growth of undesirable gut microbes [37]. Use of Curcuma longa L. rhizome is a preferred choice of Ayurvedic practitioners to restore gut microbiome, and is used to cure diseases such as stomach ulcer, ulcerative colitis, etc. [23], but the active ingredient of rhizome, curcumin, has poor bioavailability [38], and do not have effective synergic effects with other herbals/ ingredients except piperine [39], and is a matter of the future research task to establish how curcumin can be utilized more potentially as medicine [40].

Table 1.

Summarized details on gut-microbial effects of Indian traditional herbal brews

S. no	Plant name	Application and uses	Phyto-microbial properties
			Ingredients	Pharmacological properties
1	Adhatoda vasica (L.), Nees Family: Acanthaceae Traditional name: Vasaka	Decoction of the fresh leaves used as hepato-protective, for diarrhoea and dysentery treatment in Ayurveda/ Unani systems of medicines [47]	Leaves are rich in vitamin C and arotene, and have betaine, adhatodine, vasicine, vasicinol, anisotine, hydroxypeganine, adhatonine, quercetin, kaempferol, etc. [48]	Leaves extracts have a potent protective effect on the liver against carbon tetrachloride (CCl4), and D-galactosamine induced-effect, though, the concrete mechanism involved on the cellular level is not fully clear [49]. The extract of leaves in 70% ethanol has the highest ability to scavenge free radicals and has the most potent reducing power than other fractions from the species [49]
2	Andrographis paniculata (Burm.f.) Nees Family: Acanthaceae Traditional name: Kalmegh	Traditionally, the decoction of stem and leaves is used to treat stomach aches, dyspepsia, loss of appetite, dysentery, inflammation, irregular stools, diarrhea, colic pain, etc. [50]	Andrographolide, neoandrographolide,14- deoxyan-drographolide, andrographolactone, andrograpanin, flavone-1, 2’methylether, etc. [50]	Andrographolide has anti-inflammatory properties [51], and significantly increases the useful intestinal bacteria such as Lachnospiraceae_NK4A136_group, f. Lachnospiraceae_Unclassified, and Ruminococcaceae_UCG-014, and stabilises the side effects caused by amoxicillin in gut microbiota [51]
3	Asparagus racemosus Willd Family: Asparagaceae Traditional Name: Satavari	Ayurveda recommends roots of the species for female health. The roots powder is boiled in milk and drunk after filtration to strengthen the immune system and to purify blood, to treat hyperacidity, impotence, leucorrhea, menopause syndromes, etc. [52]	Steroidal saponins (Shatavarins I, IV-X), asparagamine, mucilage, isoflavones, racemosol, Vitamins (A, B1, B2, B9 C, E), etc. are present in roots, though vary in contents depending on harvesting conditions and geographical locations [53]	Species have been described in the British and Indian Pharmacopoeias [54]. A. racemosus roots increases the life span of mucus secretion cells, and their defensive factors along the cellular mucus due to antioxidant impact. The crude extracts of roots potentially reduce total acidity, free acids, and gastric juices (doses of 25–100 mg/kg for 5 days) and protect rats considerably against duodenal ulcers (50 mg/kg, twice daily) [55]. Ethanolic extract of roots enhances insulin secretion from the perfused pancreas [56]
4	Berberis aristata DC Family: Berberidaceae Traditional name: Daruharidra	The decoction of the root and stem, and its concentrated soft mass is traditionally used to treat gastrointestinal disorders, jaundice, diarrhea, etc. [57]	Berberine, berbamine, oxycanthine, palmatine, epiberberine, aromoline, jatrorhizine, dehydrocaroline, columbamine, oxyberberine, etc. are the main therapeutic ingredients [57]	Berberine has been reported as an effective gut alleviator in interaction with the gut microbiota [58]. The efficacy of aqueous extract of roots is almost equal to Warburg's tincture and quinine. Plant aqueous extract does not have any toxic effects on the brain, stomach, and other vital organs [57]. Berberine stimulates the central nervous system by inhibition of monoamine oxidase-A [59]
5	Cassia angustifolia Vahl Family: Leguminosae Traditional name: Kalyani	Traditionally, the decoction of leaves is used to treat loss of appetite and anemia, and infusion of leaves is used early in the morning on an empty stomach for three days to cure jaundice [60]	Anthraquinone glycosides (sennoside A, B, C, & D), tinnevellin glycoside, rhein-8- diglucoside, rhein-anthrone-8-glycoside, β-sitosterol, etc. [61]	Anthraquinones are used to clear the bowel before colonoscopy and inhibit a variety of bacteria and dermatomyces. Sennosides have no toxicity (up to 500 mg/kg doses in dogs, and up to 100 mg/kg in rats) [61]. Senna extract reduces metabolic disturbances, and decreases oxidative stress, and associated body ailments [62]
6	Costus speciosus (J. Koenig) Sm Family: Costaceae Traditional name: Kembuka	The decoction or infusion of leaves is used to treat diarrhea [63]	Leaves contain α-tocopherol, lupeol, β-amyrin, palmitates, α-amyrinsterate, etc. [64]	Leaves of the species have been reported for hypoglycemic properties and increased insulin activity resulting into normalization of the elevated blood glucose level [64]
7	Cuminum cyminum Linn Family: Apaiaceae Traditional name: Jiraka	Decoction of C. cyminum seeds is used to treat inflammatory, gastro-intestinal, and neurological disorders [65]	Cuminaldehyde, cymene, pinene, terpinene, thymol, fixed oil, and volatile oils [65]	The hot and saline aqueous cumin extracts along its oleoresin and essential oil have been reported to increase the activities of protease, amylase, phytase, and lipase [66]
8	Garcinia indica Choisy Family: Guttiferae Traditional Name: Kokum	Traditionally, the decoction of the fruit is used to cure diabetes [67]. Ayurveda has listed G. indica as a drug and to cure cardiac diseases [68]. Fruit juice is used to restore insulin resistance [69]	G. indica fruits have (-) hydroxy citric acid [(-) HCA], garcinol, isogarcinol, cyanidin-3-glucoside, cyanidin3-sambubioside, significant amounts of vitamin C, etc. [70]	(-) HCA inhibits the production of acetyl CoA resulting in a reduced amount of LDL and triglycerides. (-) HCA promotes synthesis of glycogen, resulting in signals to brain for fullness and satisfaction sooner due to loss of appetite [34]. Barve reported that garcinol enriched fraction (100 mg/kg) corrects dyslipidemia, inflammatory, and oxidative stress in experimental mice [70]
9	Glycyrrhiza glabra Linn Family: Fabaceae Traditional Name: Mulethi/ Yashtimadhu,	In Ayurveda, the infusion of roots is used to induce emesis [71], and roots decoction is used to cure burning sensation and anemia [72]	Roots of the species have glycyrrhizin, 18-β-glycyrrhetinic acid, glabrin A, glabrin B, sitosterol, stigmasterol, hromenes, benzofurans, dihydrostilbenes, coumestans, coumarins, dihydrophenanthrene etc. [73]	Roots of G. glabra are used as an antioxidant, antimutagen, to boosting immune functions, and preventing damage to the genetic material [34]. Glycyrrhizin is metabolized to glycyrrhetic acid, and 18-glycyrrhetic acid 3-O-mono-β-d-glucuronide by intestinal bacteria [73]. Glycyrrhizin, 18-β-glycyrrhetinic acid, and glabrin (A, B) are associated with reduced oxidative stress, anti‐inflammatory, etc. properties [73]
10	Gymnema sylvestre (Retz.) R.Br. ex Sm Family: Asclepiadaceae Traditional name: Gurmar	The decoction of leaves and stems has been used to reduce the elevated blood sugar of diabetic patients for nearly two thousand years [74]	Leaves of the species have gymnemic acids (I -XVIII), gurmarine, betain, stigmastirol, cholin, gymnenmasins (A, B, C, and D), etc. [75]	Kang et al. have reported the reduced oxidative stress from the use of ethanolic extract of G. sylvestre in diabetic rats [76] leaves of the species also stimulate the circulatory systems, heart, and uterus, and have anti-sweet and hepatoprotective properties [77]
11	Ipomoea aquatica Forssk Family: Convolvulaceae Traditional name: Kadambi/Kalambi	The decoction of leaves (to cure piles, stomach disorders, and skin rashes), and whole plant (to treat high blood pressure, constipation, stomach disorders, and liver ailments) is used [78]	Methanolic extract of the species has 50 compounds, and phytol, 1-heptacosanol, fumaric acid, tridecanal, stigmasterol, etc. are main ingredients [78]	I. aquatica resin glycosides have been reported as pancreatic lipase inhibitors and inhibit the lipolysis of high-fat food (salad with butter dressing) in the intestine [79]. I. aquatica aqueous extract (dose of 160 mg/kg) has a potent inhibition on glucose absorption compared with controlled rat models [80]
12	Momordica charantia Linn Family: Cucurbitaceae Traditional name: Karela /Tita karela	Decoction of either leaves or fruits of the species is used traditionally to treat diabetes [74]	The main therapeutic ingredients of fruits are α-momorcharin, charantin, cucurbitacins, β-sitosteryl glucoside, polypeptide-p (p-insulin), momorcidine, etc. [81]	Bai et al. have reported that aqueous extract of fruits of M. charantia decreases the population of the endotoxin-producing opportunistic pathogens and enhances butyrate producers in rats [82]. Polypeptide–p has similarly functioned as human insulin. It has been reported to lowering blood glucose levels after injecting into langurs and humans [81, 83]
13	Ocimum sanctum Linn Family: Lamiaceae Traditional name: Tulsi	Traditionally, the infusion of leaves is used to treat gastric hepatic, and cardiac disorders [84], and the whole plant decoction [85], is used to treat fungal, viral, and bacterial infections [86]	α-bisabolene, β-bisabolene, apigenin, β-caryophyllene, eugenol, eucalyptol, camphor, ursolic acid, carvacrol, cirsimaritin, oleanolic acid, rosemarinic acid, etc. are the main therapeutic ingredient of O. sanctum [86]	Ethanol extract of O. sanctum significantly affects the cytochrome P450, cytochrome b5, and aryl hydrocarbon hydroxylase [87]. Eugenol, a potential therapeutic ingredient of the species has anti-microbial properties [86] O. sanctum enhances the activity of superoxide dismutase and catalase resulting in the mopping of free radicals and other toxins [88] and reducing DNA damage [89]
14	Phyllanthus niruri Linn Family: Phyllanthaceae Traditional name: Bhumyamlaki	The infusion of the herb is used as a stomachic, appetite, anti-spasmodic, laxative, carminative, and against constipation, hepatitis B, etc. [90]	Phyllanthin, linolenic acid, hypophyllanthin, phyltetralin, ricinolic acid, niruriside, etc. are the main ingredients [90]	P. niruri plant has hepatoprotective and antiviral properties against hepatitis B. The methanolic extract of the species has immunomodulatory activity [90]
15	Piper longum Linn Family: Piperaceae Traditional name: Pippali	A decoction of P. longum fruits is orally used to cure cough, cold, and chronic bronchitis [91]	The P. longum fruits have piperine, methyl piperine, pipercide, tetrahydro piperine, etc. [92]	Piperine reduces lipid peroxidation, protects liver against CCl4, and tertiary butyl hydroperoxide-induced toxicity [92], and can regulate multiple signalling molecules [93]
16	Piper nigrum Linn Family: Piperaceae Traditional name: Maricha/ Kali Mircha	The decoction of powdered black pepper fruits is used to increase appetite, and treat stomach aches, dysentery, cough, cold, throat diseases, etc. [94]	P. nigrum fruits contain alkaloids (5–9%,) (mainly piperine, chavicine, piperidine, and piperetine), volatile oil (1.0–2.5%), and resin [95]	On oral use, P. nigrum in whole fruits, and its active ingredient piperine stimulates the digestive enzymes of intestine and pancreas and increases biliary bile acid secretion [96]. Piperine enhances the therapeutic efficacy of many vaccines, drugs, and nutrients by inhibiting various metabolising enzymes [97]
17	Plumbago zeylanica L Family: Plumbaginaceae Traditional name: Chitrak	Traditionally, the decoction of P. zeylanica roots is used as an anti-diarrhoeal, to relieving constipation, and stimulate appetite [98]	Roots have plumbagin, zeylanone, droserone, isozeylanone [99], β-asarone, oleic acid,1, 4-naphthalenedione, etc. [100]	Plumbagin reduces serum cholesterol and LDL-cholesterol levels (53 to 86%, and 61 to 91% respectively), and is a potent inhibitor of NF-kB [99]. Petroleum ether extract from roots has a protective effect against paracetamol-induced hepatocellular damage [101]
18	Psidium guajava Linn Family: Myrtyaceae Traditional name: Amarudha	The decoction from the tender leaves of species is used to treat digestive diseases and reduce blood glucose levels [74]	Leaves have quercetin, kaempferol, myricetin, hyperin, catechin, gallic acid, epicatechin, etc. [102]	P. guajava leaves aqueous extract alleviates hyperglycemia and insulin resistance (in-vivo and in-vitro) by regulating glucose metabolism and restoring the gut microbiota on oral use for 12 weeks in diabetic mice [103]
19	Terminalia arjuna (Roxb.) Wight & Arn Family: Combretaceae Traditional name: Arjuna	Hot aqueous extract of the stem bark of T. arjuna is traditionally used for cardiac health in Ayurveda [104]	Stem bark has 34% CaCO3. The main ingredients of bark are arjunin, arjunic acid, arjunetin, gallic acid, arjunoside (I, II), catechin, kaempferol, quercetin, etc. [105]	T. arjuna bark aqueous extract induces positive inotropy and accelerates myocyte relaxation and has a cardiotonic effect on ventricular myocytes [104]. Bark aqueous extract enhances SR (sarcoplasmic reticular) functions of the heart resulting in a promising and relatively safe heart and is used to treat chronic heart ailments [104]
20	Terminalia chebula Retz Family: Combretaceae Traditional name: Haritaki/ Harard	Traditionally, fruit pulp is extracted in warm water and is given to cure and control of diabetes with a single dose regularly for 30 days [74]	Catechin, kaempferol, quercetin, luteolin, rutins, chebulinic acid, corilagin, sennoside, terchebin, punicalagin, terchebulin, chebulanin acid etc. are the main therapeutic ingredients in fruit pulp [106]	The hepatoprotective of chebulinic acid via increasing superoxide dismutase (SOD) action and reduction in malondialdehyde, alanine aminotransferase, and aspartate aminotransferase levels, resulted in the protection of hepatic alterations through the initiation of stimulation pathways of Nrf2/HO-1 [107]. Chebulinic acid has anti-secretory and cytoprotective effects on gastric ulcers in aspirin, and alcohol-induced animals [108]
21	Tinospora cordifolia (Willd.) Miers Family: Menispermaceae Traditional name: Amrita, Guduchi, Giloya	Traditionally, the decoction of the T. cordifollia stem is used for controlling the blood sugar level of diabetic patients and support the immune system [74]	The main ingredients of the stem are tinosporide, tinosporaside, choline, berberine, tinosporine, magnoflorine, giloin, palmatine, etc. [109]	T. cordifolia water extract reduces the elevated levels of aspartate transaminase, gamma-glutamyl transferase, alanine transaminase, cholesterol (HDL and LDL), and triglycerides in alcoholic samples [109, 110]
22	Trigonella foenum-graecum Linn Family Name: Fabaceae Traditional name: Methi / Methika	Traditionally infusion of seeds powder is drunk to treat respiratory disorders [111]. The cold-water extract of seeds is drunk at next morning to cure the elevated sugar levels, etc. [112]	Trigonelline, gitogenin, disogenin, scopoletin, trigocoumarin, nicotinic acid, phytic acid, apigenin, gentianine, quercetin, kaempferol, diosgenin, etc. [112]	The steroidal saponins have anti-inflammatory properties. Seed extract has a potential role in GLUT-4 translocation without any toxic effect, and is effective in appetite stimulation, and checking inflammation [113], have antifungal, antidiabetic, antibacterial, antiviral, anti-allergic, antitumor, etc. properties [111]
23	Withania somnifera (L.) Dunal Family: Solanaceae Traditional name: Ashwagandha	Traditionally, fresh leaves (50 g) of the species are kept in water (200 ml) for the whole night and are used in the morning before breakfast (50 ml) to treat diabetes and overcome general debility [74]	Leaves contain total 62 compounds, in which derivatives of benzoic, caffeic, and ferulic acids, along withaferin A, withanolide A, etc. are the main therapeutic ingredients [114, 115]	Methanolic extract of leaves inhibits the growth of Gram-positive (S. aureus) and negative (E. coli) bacterial strains (10–100 μg/ml) and suppresses the development of Enterococcus species and S. aureus (1–2 mg/ml) [115]. Alcoholic extract of leaves has hepatoprotective properties in CCl4-induced alterations and inhibits ochratoxin A. Leaves are a good source of dietary fibre [114]
24	Zingiber officinale Rosc Family: Zingiberaceae Traditional name: Shunti	Traditionally, the decoction of the rhizomes is prescribed to reduce the elevated blood sugar levels in type 2 diabetes mellitus [74]	Gingerols, zingerone, eugenol, zingiberene, shogaols, α-, and β-bisabolene, etc. are the main ingredients. 6-gingerol and derivatives have highest antioxidant potential among all ingredients [116]	6-Gingerol has a potent antioxidant potential, scavenges peroxyl radicals, and has a dose-dependent inhibition of nitric oxide production [116]. Ginger and its ingredients effectively cure IBD (inflammatory bowel disease) by targeting the inflamed intestinal mucosa, blocking damaging factors (IFN-γ, IL-17, and TNFα), and promoting healing without any toxicity [117]

Indian Traditional Herbal Brews

The history of brewing herbals and their utilization in India is as old as the Rig Veda. The Vedic era reveals that a brew namely Soma, a juice (Soma-Rasa) of a sacred plant was used to maintain alertness and wise fully awakened health [41]. Further, different herbal brews have been described in the Indian traditional healing practices including Ayurveda to overcome certain body ailments which are prepared by steeping, infusion (herb in hot water for a few minutes), decoction (boiling of the herb in water), maceration, and fermentation process [42]. A most common term, ‘tea’, refers to brews from the plant Camellia sinensis L., a hot drink of leaves. Indian traditional herbal brews are non-Camellia products which are rich sources of plant secondary metabolites (alkaloids, phenolic acids, carotenoids, polyacetylenes, flavonoids, coumarins, terpenoids, saponins, etc.) and are characterized for a diversified biological impact such as anti-inflammatory, antibacterial, antioxidant, antiallergic, antiviral, vasodilatory actions, antiaging effect, etc. [43]. Though, herbal brews are consumed globally, and a few have more specific properties than others depending on their site of cultivation and are more in demand [42]. India has 17,000 plant species, 17.47% of the world, and from which 44% are known to have medicinal values [44]. Indian traditional herbal brews are prepared from different plant parts, namely stem, leaves, fruits, roots, flowers, and buds [43].

Different Chemical Classes in Herbal Brews

Indian traditional herbal brews have been widely sipped by locals for their medicinal impact for centuries and recently, these brews have attracted extended attention for their therapeutic and preventive attributes to cure and protect the body ailments due to changed dietary lifestyles, and daily activities. Leaves, buds, flowers, fruits, rhizomes, and roots of medicinal plants are used either alone or in combination to brew their ingredients which have many biotic applications, such as anti-inflammatory, anti-oxidation, anti-diabetes, antibacterial, anti-cancer, ant-viral, etc. The main chemical classes of these brews are alkaloids, flavonoids, polyphenols, organic acids, terpenoids, different vitamins, polysaccharides, etc. [45, 46], and are unique combinations of different ingredients of Indian traditional herbal brews which are tabulated in Table 1.

Natural polyphenols are mainly used in the body as an anti-oxidation and to improve insulin resistance [118]. Flavonoids, a major part of herbal brews, are mainly used to reduce the damage induced by oxidative stress in cells. Terpenoids are known for their anti-inflammatory, antimicrobial, anticancer, and antiallergic properties [119, 120], and alkaloids reduce fungal and bacterial infections [120].

Herbal Brews Inside the Human Gut

The interaction of gut microbiota with herbal brews results in several biomolecular alterations and generates a series of metabolites such as indole derivatives, vitamins, polyamines, and SCFAs. These metabolites are used to regulate homeostasis and engage with body ailments [121]. Ingredients of herbal brews interact with viruses, bacteria, archaeons, and eukaryotes (about 10¹⁴ microorganisms) in the intestine [2], and SCFAs are synthesized by gut microbiota de novo via. esterification, oxidation, glycoside hydrolysis, ester hydrolysis, reduction, isomerization, rearrangement, condensation, and intramolecular cyclization [122] primarily in the large intestine that has escaped absorption and digestion in the small intestine [123]. Though the human body does not produce enzymes to catalyse the fermentation of carbohydrates, gut microbiotas secrete a series of enzymes (propionaldehyde dehydratase and propionate-CoA transferase) to convert carbohydrates into SCFAs [124]. Acetate, butyrate, and propionate are the main SCFAs (≥ 95%), whereas caproate, valerate, formate, etc., are the remaining [125]. Bacteroidetes mainly produce propionate and acetate, and Firmicutes generate butyrate [126] in the gastrointestinal tract. Acetate is produced by bacteria via acetyl-CoA pathway and Wood-Ljungdahl pathway [124], propionate is produced via acrylate route, succinate route, and propanediol route [127], and butyrate via the butyryl-CoA: acetate CoA-transferase pathways and the phosphotransbutyrylase/butyrate kinase pathways [124, 127]. SCFAs increase the proliferation and differentiation of colonocytes, cell membrane assembly, and mucosal cell migration, and protect colonic epithelium [128], and intestinal diseases such as Crohn’s disease, colorectal cancer, and ulcerative colitis. SCFAs potentially reduce the growth of Salmonella [129], and butyrate is metabolized in epithelial mucosa and is used in the protection of the colon [128]. Acetate and propionate pass across the liver via epithelium where most of the propionate is biologically utilized but acetate remains in the circulatory system [127].

Molecular Know-How and Bio-Pathways

The gut enterotypes are not static and vary from person to person. The gut microbiota is composed of more than 1,000 different microbial species, and its microbial composition can alter throughout life [130]. Host-based alliance of the gut microbiota can be categorized as beneficial, neutral, and pathogenic in nature, and their interaction may result in the development of more potent metabolite or may be available more in number for biological functions, and generate by-products (such as n-butyrate, and SCFAs) [130]. The imbalance between the generation of the antioxidant compounds and insufficient quenching moieties resulting in oxidative stress [131], is counterbalanced by the timely intake of herbal brews as gut microbes can turn on immune cells in the gut wall resulting in the release of proinflammatory cytokines which affect the permeability of the blood–brain barrier [132]. An imbalanced microbiome can cause psycho-biotic disease, for which several therapeutic approaches including diet, prebiotics, probiotics, antibiotics, FMT, and personalized nutrition-based treatments are currently in practice [23].

Herbal Brews and Human Gut

Human Gut Microbiota in Well-Being and Disease

Human psychophysiology is collectively influenced by the microorganisms residing in various parts of the body, especially in the gut. Factors such as diet and digestion mainly influence the composition of the gut. The oral route is a usual mode of feeding and eating, though molecules of more than 0.4 nm diameter are poorly passed through the intestinal epithelium. Specific transporters from the gut to the circulatory system for individual therapeutic ingredients have been reported as the cause of their low bioavailability [130]. In the gut, generally, gut tissues and bacteria interact to keep alive a bio-equilibrium along the biological, mechanical, chemical, and immune barriers for invading pathogens, and have a potent impact on metabolic activities. Human intestinal tract metagenomics has revealed nine bacteriophyta in the human intestine, namely Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, Cyanobacteria, Verrucomicrobia, VadinBE97, and Spirochaetes [133]. In gut microbiota, different bacterial strains produce different enzymes such as β-D-glucosidase, β-galactosidase, β-D-glucuronidase, β-xylosidase, azoreductase, nitroreductase, and α-L-rhamnosidase [133] which metabolize the active ingredients of ingested food and feed (Fig. 2). The change in gut microbial composition leads to metabolic disorders and enhances oxidative stress and inflammatory activities resulting in deterioration of normal health associated with diseases such as cardiovascular ailments, hepatic disorders, rheumatoid arthritis, Alzheimer's, Parkinson's, inflammatory bowel diseases, etc. [130].

Fig. 2.

A. vasica, P. guajava, T. arjuna, T. chebula, and T. foenum-graecum, all five species commonly contained kaempferol and quercetin. Kaempferol and quercetin have been reported for their growth inhibitory effect on phylum Bacillota (E. cylindroides, Erysipelotrichaceae, Bacillus, and Enterococcus) and harmful Fusobacteriota on the gut microbiota. These species are also responsible for colon cancer. Kaempferol and quercetin enhance the growth of phylum Bacillota (Lactobacillus and Clostridia), Bacteroidota, and Actinomycetota (Bifidobacterium, Bifidobacterium adolescentis), and support the beneficial gut microbiota. Additionally, all five species are pharmacologically active as hepatoprotective, anti-diabetic, anti-diarrheal, and potent antioxidant agents displaying gut-microbiome axis interaction with organs (e.g., liver, pancreas, and intestine)

The result of oral ingestion of specific items like Indian traditional herbal brews used to overcome disturbed gut microbial composition, the gut microbiota increases the therapeutic activity of the bio-active molecules, and reduces the toxicity of certain ingredients by different reactions such as hydroxylation, methylation, esterification, decarboxylation, etc. Such derivatives are significantly less toxic and therapeutically more potent compared to the parental compound [134]. Further, the use of herbal brew with berberine increases the abundance of butyrate-producing bacteria resulting in reduced blood glucose and lipid levels and affects the composition of short-chain fatty acids [135] and prevents fatty diet-induced diabetes and obesity. Though the molecular knowledge in detail is not established for all the brews (Table 1), certainly patients have benefited from the disturbed gut microbiota and associated ailments (Fig. 3) for thousands of years without side effects.

Fig. 3.

Multiple tasks of Indian traditional brews to gut microbiota balance and better health

Gut Microbiota and Food Habits

The gut has non-pathogenic bacteria, which help in the prevention of settlement of harmful microorganisms, metabolize food nutrients and medicine along the protection of intestinal function. The gut gets colonized by micro-organisms in utero, and is largely blessed by the mode of delivery, but gains 40–60% with the adult microbiota at the age of 3 years [136]. Diet is a deciding for the richness, composition, and diversity at every stage of life, though a vegetable and fruit-rich diet is associated with a healthy gut microbiota. Animal-based diets have resulted in a reduced number of Firmicutes with an enhancement in bile-tolerant organisms [136]. Jandhyala et al. have concluded that a diet rich in dietary fibers promotes gut microbiota health [136], and obesity is associated with increased numbers of body ailments [137].

Gut Microbiota and Mental Health

There is a bidirectional information transmission arrangement between the brain and gut, and most of the exchange occurs directly through the vagus nerve to regulate many internal functions. Another channel is by means of different chemical messengers, such as hormones, neurotransmitters, and peptides, in which many more neurotransmitters and peptides are produced by the gut itself, and many of these are also found in the brain. Gut microbiota may affect the secretion of these gut-derived ingredients, including serotonin and dopamine, and can develop unique chemical agents that may enter the bloodstream and affect different body parts including the blood–brain barrier, and can cause anxiety-linked depression-like behaviors [23, 138] while butyric acid improves the body immunity [23]. Gut and gut bacterial health is also affected by the cortisol, secreted by adrenal glands under a stressed condition by brain-triggered stimuli, which increases intestinal permeability, results in a leaky gut, and shuts down the gut immune system [139]. Ayurveda recommends the W. somnifera to reduce mental stress (Fig. 4), which has a potential impact on the healthy gut microbiota [23].

Fig. 4.

In the brain-gut-microbiome axis, most of the transmissions are directly through the vagus nerve, though another channel for transmission is via chemical messengers, such as hormones, neurotransmitters, and the gut itself, which produces peptides. Many of these peptides are also found in the brain. Enterococcus species and S. aureus may affect the secretion of these gut-derived ingredients, including serotonin and dopamine. They produce unique chemical messengers that may enter the bloodstream and affect different body parts including the blood–brain barrier causing anxiety, stress, and inflammation. W. somnifera reduces mental stress, has anti-inflammatory effects, and suppresses the development of Enterococcus species and S. aureus

Polyherbal Composition and Gut Microbiota

The use of brew from a combination of two or more herbs is widely used in Indian traditional practices such as the combination of P. nigrum, O. sanctum, and Z. officinale is used as an anti-inflammatory, immunomodulator, and bioavailability-enhancer in traditional systems [140]. Both O. sanctum and Z. officinale have higher prebiotic activity compared to the fructo-oligosaccharide (FOS), a standard prebiotic [141]. P. nigrum, O. sanctum, and Z. officinale are used to reduce systemic inflammation [142]. Narendra Babu et al. have reported that the hydro-alcoholic extracts of P. nigrum, O. sanctum, and Z. officinale enhanced the growth of beneficial bacteria, Lactobacillus rhamnosus, and Bifidobacterium infantis, [141], and have prebiotic potential, and both are used for gut bacterial alterations [140].

Ayurvedic formulation namely Triphala (a mixture of equal quantities of fruits of Emblica officinalis Geartn., T. bellerica, and T. chebula) is used to maintain the health and rejuvenate it, more particularly to ease the elimination process. Clinical results have revealed that Triphala enhances the appetite and reduces constipation and hyperacidity with biological impacts such as immunomodulatory, anti-inflammatory, antimutagenic, hypoglycemic, antibacterial, adaptogenic, and antioxidant. The phenolics in Triphala can attenuate the human gut microbiome and enhance the growth of beneficial Lactobacillus and Bifidobacteria with inhibition of the growth of undesirable gut microbes [23].

Uniqueness of Indian Traditional Herbal Brews

Rhythm-Based Applications

Indian traditional healing system is based on daily routine (Dinacharya), seasonal routine (Ritucharya), and lifetime routine (Asrama) which is also recognized by modern medicine as biological rhythms and has been explained with genetic basis from bacteria to humans with all forms of life as an internal ‘biological clock’. Aggression on natural rhythms creates health ailments as has been noted among shift workers with higher incidences of digestive disorders, obesity, psychiatric, cognitive impairments, cardiometabolic stress, etc. [143]. Further, a disturbed circadian rhythm of certain cells in the liver and intestine due to immediate sleep after the meal compared to the rest of the body is an alarm to digestive health and a time restriction of 2 h duration to sleep the body after the meal [144]. A germ-free mouse develops both glucose intolerance and obesity on the transfer of gut bacteria from jet-legged mice who were forced to walk during the day times revealing that gut bacteria also have daily rhythm [145], and seasonal biorhythms [146].

Traditionally, the infusion of leaves of C. angustifolia is used early morning on an empty stomach for three days [60], and warm water extract of T. chebula fruit pulp is used with a single dose regularly for 30 days [74], Use of the cold water extract of seeds of T. foenum-graecum at next morning [112], and fresh leaves of W. somnifera steeped in the cold water is used in the morning before breakfast [74], etc. are time-based eating and feeding frequency to cure various body ailments (Table 1).

Ancient Antibiotic Analogues

Islam et al. have reported that daily intake of a mixture of 3% tulsi and 1% clove powder extract improves the feed intake, feed efficiency, carcass weight, weight gain, and gut health of broilers, and concluded that the combination of clove and tulsi (1:3, w/w), a dose-dependent therapy, and can be used as a potential alternative antibiotic as well as a growth promoter, a common brews in the Indian sub-continent [147]. The decoction of A. paniculata, a ‘natural antibiotic, used before the discovery of modern antibiotics, has antibacterial, antipyretic, and anti-inflammatory properties [148]. As there has been no new antibiotic on the market for more than 35 years already [149], and so there is an array of hopes for the species to cure the gut and reboot the microbiota as a future medicine.

Herbal brews are an excellent substitute for nano-silver as an antiviral and antibiotic agent, as its use has been proven to induce cancer, heart diseases, cytotoxicity, and delays in wound healing. Herbal brews have potent antiviral, antioxidant, and antimicrobial properties, and can eliminate pathogenic microorganisms with radical scavenging ability. The scavenger ability of these herbal brews is different for different kinds of bacteria [150]. Generally, herbal brews block reactive oxygen species (ROS) generation resulting in a direct antioxidant and can inhibit the planned cell death pathways. As herbal brews reduce the concentration of ROS in the defence mechanism before activating the apoptosis pathway, therefore, herbal brews are less toxic and have the least side effects compared to synthetic antimicrobial compounds. The high antioxidant and antimicrobial ability of these brews is beneficial to fasten the healing of all types of wounds and has been proven a high antimicrobial moiety at a low price [32].

Significance and Research Avenues

Biomolecular studies on Indian traditional herbal brews used for a healthy gut microbiota have revealed it as a platform of ancient practices to lengthen the life span that may result in globally accepted modern green herbal brews, and a choice to maintain natural health. Though, poor bioavailability of the hot milk brew of C. longa rhizome, a potent Indian traditional brew is used to treat various body ailments [40], needs a focused investigation to enhance its bio-absorption and determine its effects on the microbiome of different individuals. Although black, green, and oolong teas are the most consumed, globally, the traditional uses and acceptability of Indian traditional brews are intact for curative and preventive purposes for different body ailments [151], mainly due to their antioxidant potential to improve aging-related ailments [152]. The addition of vitamins has been reported to maintain the antioxidant status of these brews [153].

Although herbal brews have many health benefits and are considered safe, clinical data are not available on the interactions and toxicity, a regulatory issue [154]. Moreover, medicinal plants used as raw material for brews can be infected by fungi and mycotoxins during the harvesting, storage, and transportation process [155], and may have collected from relatively harsh environments, or industrialized zones resulting in high concentrations of heavy elements, and pesticides [156, 157]. The fruit pulp of Syzygium cumini (L.) Skeels collected from India have different biological properties under similar experimental conditions from the pulps of Brazil due to different chemical compositions [42]. An established specification is a parameter to avoid the inferior quality of herbs along with adulterants, as both have an impact on their safety and pharmacological effects [120].

The sensory quality of these traditional brews has scope for innovation by improving taste without compromising efficacy [120]. Characterization of the active ingredient and their synergistic chemistry is a major task [158] to be completed for the global acceptance of these brews. The therapeutic role of trace compounds or elements is quite valuable because of their synergistic effects, though tedious to identify as an entirely new entity on purification from the complex herbal mixture [120].

The therapeutic potential of Indian traditional herbal brews as antiviral activity, and instructions of the Ministry of AYUSH, Govt. of India to use against the COVID-19 virus [159] reflects the needs and scope for innovation on all brews mentioned in Table 1.

Conclusion

Literature screened for 24 herbs used as brew for gut microbiota balance in Indian traditional practices has revealed that kaempferol and quercetin are common in five, and berberine and piperine in two different plant species. Additionally, the uses of these brews have resulted in good health even for patients with liver and heart along the enhanced body immunity, though bio-molecular pathways are mostly unclear. Research data for each herb with the recommended volume of brew, limit of its TDS (total dissolved solid) content, and toxicity, if any may lead to their utilization as ‘modern green medicine’, and to develop more potent products in the future. An industrial market beyond traditional and folklore may be developed by patentable products along with the geographical indication (GI) tags, as natural and low-cost raw material to maintain a healthy gut microbiota.

Author Contribution

DDJ: Conceptualization, Writing—Original draft preparation, RS: Methodology, Data curation, Reviewing and Editing, LD: Visualization, Investigation, KK: Reference Compilation, BGS: Editing and Visualization, VSR: Reviewing and Editing. All authors have read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.