The Gut Microbiome

The Gut Microbiome – some top Phytotherapy Options

Posted: May 2024

Author: Phil Rasmussen | M.Pharm., M.P.S., Dip. Herb. Med.; M.N.I.M.H.(UK), F.N.Z.A.M.H.

Introduction

A large proportion of phytomedicines have indications involving gastrointestinal ailments. Of course, their pharmacological actions and clinical indications are diverse, but of growing interest, are their influences on gut health. Also, their influential impact on the community of microbes that live within our digestive tract, known as the gut microbiome.

Intestinal microbiota have a crucial role in the activation and metabolism of medicinal plant phytochemicals to simpler and bioavailable molecules, including active metabolites. Virtually all polyphenolic compounds such as flavonoids, anthocyanins, saponins and coumarins, occur in glucosidal forms. Prior to being used they must be metabolized to release their active orally bioavailable components.

Human digestive enzymes are usually unable to perform this function, whereas enzymes produced by gut microorganisms can. While these biotransformation interactions are complex and still poorly understood, it is evident that the makeup and health of the individual gut microbiome can significantly influence oral bioavailability of active phytochemicals, and thus clinical outcomes.

These interactions are two way, as the consumption of plant polyphenols and carbohydrate compounds can have a prebiotic effect, and lead to increased levels of beneficial bacteria. Gut microbial modulation as a mechanism through which therapeutic actions are produced by medicinal plants, is a huge and rapidly emerging area of research ^(1-3).

While tannins are too large to be absorbed in their original state from the gastrointestinal tract, they can be hydrolysed by microbiota to produce smaller, bioavailable, and bioactive metabolites, with many beneficial effects on health. Supplementation with certain tannins has also been found to increase the diversity and abundance of beneficial butyrate-producing and probiotic bacteria and amino acid metabolism ⁽⁴⁾.

Regular ingestion of medicinal plants such as Peppermint, Green tea and Baical skullcap can increase the number of unique bacterial genera and change the relative abundances of particular species ^(5-8).

A healthy gut microbiota helps to reduce and prevent colonisation by enteric pathogens through competitive exclusion and the production of bacteriostatic and bactericidal compounds. Phytomedicines, through enhancing the production of desirable species within the microbiota, can therefore help in the management of unwanted infections ^{(9, 10)}.

Many studies have associated changes in the gut microbiota composition by various traditional Chinese medicines, with a lower risk of development of metabolic disorders such as diabetes type 2 and obesity. Apart from dietary and lifestyle factors, medicinal plants are increasingly associated with protecting against these chronic and increasingly common conditions ^(11-14).

Potential influences of our gut microbiome on mental health and wellness are also being revealed through new findings on an almost daily basis. Correlations between the gut microbiota and several mental health conditions have been reported, and the gut and brain are in constant bidirectional communication, forming the so-called gut microbiome-brain axis. Protective effects against conditions such as anxiety and depression, through dietary or phytomedicine interventions that enhance beneficial gut microbiota while suppressing harmful ones, have been implicated ^{(3, 15)}. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability.

While a very large number of polyphenol rich plants are likely to be associated with fostering a healthier gut microbiome, there are some standouts worth highlighting.

Coptis (Coptis chinensis)

Roots and rhizomes of Coptis have been used in Traditional Chinese Medicine to treat digestive, respiratory, and infectious disorders for more than 2000 years.

Coptis demonstrates antiviral, antibacterial, hypoglycaemic, hypolipidaemic and weight loss enhancing properties, and traditional uses include for syndromes involving abdominal pain and diarrhoea. It also has protective effects against sepsis, a dangerous state which is related to gut dysbiosis and a disordered immune response to microbial infection ^{(16, 17)}.

Coptis is also traditionally used for diabetes, due to its numerous influences on glucose metabolism and its ability to ameliorate insulin resistance through different mechanisms of action. Several of these have been related to its regulation of intestinal hormones, and modulation of the gut microbiota ⁽¹⁸⁾.

The intense golden colour of Coptis rhizomes is attributable to its rich content of the isoquinoline alkaloid berberine. Huang lian, the Chinese name for Coptis, literally translates to “yellow thread”. Berberine is also found in related plants such as Barberry (Berberis vulgaris) and Golden Seal (Hydrastis canadensis) and has a wide and impressive spectrum of pharmacological activities. These include anti-diabetic, anti-obesity, anti-inflammatory, antioxidant, immunomodulatory and antimicrobial properties. The oral bioavailability of berberine, however, is low, but research is increasingly revealing its many interactive relationships with the gut microbiota.

These include the biotransformation of berberine itself to produce active metabolites with similar pharmacological effects by microbes within the gut, as well as berberine-induced alterations in the composition and metabolism of the gut microbiota composition ^(19-20). Its benefits in diabetes type 2 and prevention of obesity, have been linked with structural modulation of the gut microbiota and a resulting increased short-chain fatty acid-production ^{(21, 22)}.

Berberine’s effects in hyperlipidemia, atherosclerosis, liver diseases, intestinal diseases, mental disorders, autoimmune diseases, and thrombosis, have all been associated in some way with the effects it and related alkaloids have on the gut microbiota ^{(23, 24)}.

Other phytochemicals apart from berberine contribute to Coptis’s actions. In animal models of ulcerative colitis, both berberine and total Coptis alkaloids decreased levels of the pathogenic bacteria Bacteroides acidifaciens and increased those of the probiotic Lactobacillus spp., but total Coptis rhizome alkaloids exhibited superior effects ⁽²⁵⁾.

The polysaccharides found in Coptis also seem to influence the intestinal flora to promote the secretion of interferon and other anti-inflammatory cytokines from intestinal Peyer’s patches⁽²⁶⁾. A combination of Coptis polysaccharides and berberine had synergistic anti-inflammatory effects in ulcerative colitis, these being correlated to an increased relative abundance of short-chain fatty acid producing bacteria, improvement in tight-junction microbiota, and secretions of inflammatory and anti-inflammatory cytokines ^{(27, 28)}.

The use of a Coptis and Magnolia (Magnolia officinalis) combination to treat gastritis, has been associated with regulation of the intestinal microbiota as a precursor to anti-inflammatory effects ⁽²⁹⁾.

Barberry (Berberis vulgaris)

Berberine is also abundant in various Berberis species found throughout the world, including common barberry (Berberis vulgaris), Berberis aristata, Berberis darwinii and Berberis kansuensis. Barberry is used for wide ranging purposes in traditional medicine, and exerts beneficial effects in several inflammatory, oxidative, and immune-related diseases. These include diabetes, obesity, cardiovascular diseases, neurodegenerative diseases, autoimmune diseases, allergic diseases, and infections ⁽³⁰⁾.

As with Coptis, its usefulness in the treatment of diabetes type 2, has been linked with modulatory effects of berberine on the gut microbiota. They include an increased abundance of Bacteroidetes, and a decreased relative abundance of Proteobacteria and Verrucomicrobia. The probiotic Lactobacillaceae is also significantly upregulated by berberine and Barberry, this being negatively associated with the risk of type 2 diabetes mellitus ⁽³¹⁾. Similar influences on the composition of the gut microbiota, have been suggested as mechanisms of antidiabetic effects in animal studies by Berberis kansuensis ⁽³²⁾.

Potential applications in multiple sclerosis, through modulatory effects of berberine on the function and numbers of T cell subsets and dendritic cells, as well as cytokines involved in this neurodegenerative condition, have recently been reported ⁽³³⁾. A methanolic extract of the stembark of Berberis darwinii is a potent inhibitor of the enzyme acetyl cholinesterase, implicating potential applications in the prevention or treatment of Alzheimer’s disease ⁽¹⁹⁾.

Baical Skullcap (Scutellaria baicalensis)

Baical skullcap has also shown several beneficial activities that influence the gut microbiota in animal studies ^{(34, 35)}. These include inhibiting the growth of some potential enteropathogenic and inflammation-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella and Enterococcus. Promotion of the proliferation of beneficial butyrate-producing bacteria such as Lachnospiraceae and Prevotellaceae, has also been reported ⁽³⁶⁾.

A polysaccharide from Baical skullcap produced numerous positive effects in a mouse model of ulcerative colitis, including reduced weight loss and colonic pathological damage, and a lowering in levels of proinflammatory cytokines. Additionally, the intestinal barrier was repaired. The abundance of Firmicutes, Bifidobacterium, Lactobacillus, and Roseburia were significantly increased with the polysaccharide treatment, while levels of Bacteroides, Proteobacteria and Staphylococcus, were reduced ⁽³⁷⁾.

An eight-week Korean clinical trial involving a combination of Baical skullcap with the drug metformin, reported additional improvements in glucose control and inflammation through addition of the medicinal plant to the treatment regimen of patients with type 2 diabetes mellitus ⁽³⁸⁾. Remarkable increases in Lactobacillus and Akkermansia levels in the gut microbiota were associated with Baical skullcap treatment.

Other research has shown anti-inflammatory, intestinal permeability and gut microbiota modulating effects in association with hypoglycaemic actions, using a combination of Baical skullcap with Coptis, in diabetic rats ⁽³⁹⁾. Potential applications in the treatment of obesity, have also been reported, with microbiome modulation as a key mechanism ⁽⁴⁰⁾.

Green Tea (Camelia sinensis)

Many health promoting effects of green tea seem to be related to its inter-relation with the gut microbiota ⁽⁴¹⁾. Gut bacteria can metabolise larger polyphenolic green tea compounds into smaller bioactive molecules with antioxidant activities. Green tea has been reported to correct microbial dysbiosis that is now known to be a factor in conditions such as obesity or cancer ⁽⁴²⁾.

Several human clinical trials have associated health benefits of regular green tea intake, with an influence on the gut microbiota. These include a recent American study involving 294 participants with abdominal obesity and dyslipidemia who consumed green tea daily together with a Mediterranean diet. This led to beneficial changes in body weight and cardiometabolic biomarkers, and prominent compositional changes in the gut microbiome, largely driven by the low abundant, “non-core,” microorganisms.

They included enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis ⁽⁴³⁾.

Some Native Plant standouts

Many of our native plants are also rich in polyphenolic compounds and are likely to influence our gut microbiome favourably. Several are traditionally used for the treatment of gastrointestinal tract infections. Amongst these, species including Mānuka, Kānuka (Kunzea ericoides), Harakeke (Phormium tenax), Horopito (Pseudowintera colorata), Tanekaha (Phyllocladus trichomanoides), Totara (Podocarpus totara) and Pukatea (Laurelia novae-zelandiae), all exhibit good activity against specific pathogens. These and other native plants whose actions may be mediated through influences on the gut microbiome, ^44.44.

Mānuka

The powerful astringent and antimicrobial effects produced by infusions and hydroethanolic liquid extracts of Mānuka’s leaves and stems, make it useful in the treatment of gastrointestinal infections. Mānuka itself contains a powerful antimicrobial essential oil, is a rich source of tannins, and exhibits bactericidal activities against several pathogens including Escherichia coli, Staph aureus, and Candida albicans ^(45-49). The antimicrobial and anti-inflammatory properties of leaf and stem extracts have been researched and promoted by Phytomed since the launch of the company in 1998 ⁽⁵⁰⁾. Antioxidant and diverse disease modifying influences through regular intake of these, like those of Green Tea, are likely. As with other medicinal plants traditionally used for such digestive tract disorders, gut microbiome modulation is likely to be a key mechanism of Mānuka’s action.

Some other natives

Rebalancing of different microbial species within the gut, is also probably involved in the highly regarded anti-diarrhoeal and anti-inflammatory properties of leaves of our well known Koromiko (Hebe stricta). This has a long traditional of use in Rongoā Māori and was used for diarrhoea and dysentery among Māori and European settlers, including by New Zealand Soldiers during the Second World War.

Horopito (Pseudowintera colorata) and Akeake (Dodonaea viscosa) also exhibit astringent, anti-inflammatory and antimicrobial properties. Hydroethanolic extracts when taken internally and depending on dosages and the clinical situation, will almost certainly impact population levels of some microbiome species in a negative manner, and promote the growth of others ⁽⁴⁴⁾. An Indian variety of Dodonaea viscosa has been shown to be gastroprotective in animal studies ⁽⁵¹⁾.

Hoheria (Hoheria populnea), our native alternative to Slippery Elm and other polysaccharide hydrocolloid rich plants, can help reduce symptoms of dyspepsia or gastritis when taken either as an infusion or hydroethanolic liquid extract. These polysaccharides, like those of Coptis, Baical skullcap, Ribwort, and numerous other medicinal plants, are likely to have prebiotic and other beneficial effects on the gut microbiome, as one of the mechanisms of action in these digestive conditions.

Summary

Many medicinal plants possess evidence of having significant prebiotic properties, and studies are increasingly suggesting that many of their therapeutic properties are likely to be at least partially attributable to their ability to modulate the gut microbiota. Resulting outcomes include improvement in colonic epithelium function, reduced inflammation, and protection from or recovery from opportunistic infection.

The bioavailability of many active phytochemicals is also highly dependent on their release from larger plant constituents or conversion to active metabolites by microbes in the gut. In addition to clinical studies to investigate therapeutic properties of probiotics, more well designed clinical trials using phytochemically characterised plant preparations and accompanied by microbiota assessments, will further inform us about the extent and nature of these albeit complex interactions, between our herbal extracts, and the gut microbiota.

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