Vittoria Battaglia

Medical Herbalist MCPP, MNIMH.

iii. Microbiome: Pro, Pre, Post.., & Phytobiotics for sleep?

Sleep Medicine..?

Part I. Part II

Back in Part I it was considered that the gut is alike the liver., in that it has a critical role in the metabolism [of nutrients, proteins, fats, oral drugs…] once they have made contact with the colon microbes. In the same way, the enzymes of the gut microbiota (oxidase, reductase, glycoside hydrolase…) can metabolise the mixtures of the many plant chemicals that are present in medicinal plants1. As we shall see., in some cases, due to higher molecular weight and polarity, these are not easily absorbed in the upper gastrointestinal tract (GIT). So., many may undergo extensive first-pass metabolism, followed by biliary secretion2.

Ultimately., the enzymes of the gut bacteria may decompose the plant compounds. This then releases the metabolites with their medicinal action profile., establishing the improved gut environment through either reorganising and repopulating the community of [beneficial] bacteria., or through an altered, more bioavailable structure., that now has a better improved potency or a reduced toxicity, enabling them to better exert their medicinal plant actions 3, 4.

There are many medicinal plants that have widely documented antimicrobial (antibiotic-like) effects, (e.g. Zingiber officinale Roscoe, Plantago lanceolata L.) 5, 6, 7. These may improve the general environment first-hand, and contribute to managing various symptoms by reducing pathogenic bacteria 8.

So., we have been able to see that there are various pathways for phytobiotics to in fact., be able to exert their therapeutic properties to improve some of the often related contributing factors., to a better quality sleep.

The multiple pathways that have been discussed, lead us to selecting the most appropriate plant constituents in which we can most effectively target the topic of sleep health, both directly through phyto-psychobiotics, and by promoting the neuroprotective effects via improvement of the microbiome.

It is possible, that the most likely consideration that would come to mind here for most of us (whether you know it under these terms or more generically), are the prebiotic effects of the polysaccharides and polyphenol containing plants., particularly lignans, flavonoids and tannins. Some research even suggests that polyphenols have dual-acting properties. As duplibiotics., these are thought first to have the antimicrobial action., cleansing and inhibiting some of the harmful microbes that can cause disease, and then they positively enhance the growth of beneficial bacteria, as a prebiotic 9.

The mechanism of action for these categories, is likely through the direct interaction that is thought to take place between the polyphenolic compound, and the microbiota. This is because their glycosides, esters and polymers, are not readily absorbed in the small intestine, making the metabolite products able to reach the systemic circulation, and exert therapeutic effect9. In the example of mucilage that we saw in Part II, it is perhaps understandable., how this direct action can be very desirable in the disturbed gut environment., as the protective and soothing demulcent effects from plants such as P. lanceolata, containing their mucilage polysaccharides (arabinose and galactose)., as they are not being absorbed, they are able to form a protective layer for the mucosa, helping to prevent invasion from local irritations10.

However, in examples such as Almond (Prunus persica (L.) Batsch.), that contains an abundance of polyphenols (mainly being hydrolysable tannins and flavonoids)., we in fact find that they are easily metabolised at the gut. Almond seeds have been found to exert positive effects in reducing depression and anxiety, as well as modulating metabolic associations such as ‘post-lunch memory decline’ through increasing the amounts of SCFA-promoting bacteria 11, 12. Interestingly, a prebiotic effect of the almond when prepared with the skin of the seed intact, did not appear to be present with un-skinned preparations. Therefore, this particular effect on the microbiota, may be largely due to the dietary fibre that is contained within the skin, as opposed to the actions of the polyphenols13.

Well-documented anxiety-reducing effects of Schisandra chinensis (Turcz.) Baill. (which is rich in polysaccharides) that is frequently implicated in cognitive and anxiety disorders and has also been found to show possible associations to hippocampal neurogenesis (the forming of new neurons in the brain)., have shown lignans to be the main effective constituent. This is partly understood to be related to the plants’ direct microbiome-gut-brain connection, and partly related to its potential to reduce the harmful bacteria in the gut through producing SCFA’s 14, 15.

The generally antioxidant and neuroprotective flavonoid groups of plants., are also not absorbed through the large intestine, again potentially interacting with microbiome as they are able to be taken up by the gut bacteria as prebiotic effectors 16. These plant groups are largely produced naturally to reduce infective bacteria; therefore, an antimicrobial activity will contribute to the composition of the microbiome. Many flavonoid groups have also shown an affinity for the GABAA receptors’ benzodiazepine binding-site, as they are able to cross the blood-brain barrier, therefore may also have beneficial effects as psychobiotics for depressive symptoms 17. Certainly, the widely documented plant medicine that is frequent for mild/ moderate depressive disorders Hypericum perforatum L. (St John’s wort), being rich in flavonoids, has also been studied for its pharmacological effects, being largely due to the role of its gut microbial metabolization 18.

Mood and calmness, and cognitive-promoting effects of flavonoids, have further been studied extensively in grapes (Vitis vinifera L.) 19. The seeds., containing condensed tannins, are shown to promote changes in the gut that reduces dysbiosis. Along with anthocyanins, flavonoids are abundant in both the peel, and in the fruit of the plant.

In fact., positive effects on the gut composition, have been well-documented across many studies of V. vinifera, that is shown to be effective particularly in promoting the proliferation of the beneficial bacteria, by altering various microbial strains that are present. It is certainly of interest though., that the strains in which were altered with the V. vinifera application, despite varying through many of the documented studies, each however reached to the same concluding outcome, even though no consistently formal target-bacteria was identified, in which to do so. For example, some found that this was achieved through increasing Lactobacillus and Bifidobacterium whilst reducing the Faecalibacterium prausnitzii and Bacteroidetes 20, whilst conversely, others found that the same effects were achieved, through either little or no relative alteration of the Bifidobacterium, and instead increasing the Faecalibacterium prausnitzii 21.

Humulus lupulus L, (hops) is a well-documented herbal medicine for sleep disorders and anxiety22. As well as containing gut-modulating flavonoids, extracts also contain antimicrobial derivatives, lupulones and humulones that have been shown to promote Enterobacteriaceae growth, whilst inhibiting butyrate-producing genera eubacterium, and probiotic Bifidobacterium. Reducing butyrate ratio in dose-dependent concentrations of Hops, in turn alters the composition of the microbiome 23.

These kinds of findings may [remind us] suggest., that rather than requiring the straight-forward increase., or perhaps even reduction of particular bacterial genera that will simply enable the supplementation of what we often presume is merely a case of deficiency in the particular strains., but instead shows where the community, ratio or balance, provides the therapeutic variable.

Therefore, the desired mechanisms of actions., may be better-suited where selectivity, and multiple interactions with the surrounding environment, may in fact be where the best outcomes are found for the desired treatment effects, in re-establishing a balance within the microbiome.

An increase of the levels of SCFA’s butyrate as well as acetate, has been shown to exert positive effects on hormone-related mental health symptoms in women, through treatment with isoflavone-rich Soybean (Glycine max (L.) Merr.) 24.  Likely contributing explanations for this effect, are thought to be due to the combinations with high level of saponins, such as Soyasaponin I. 

Particularly, triterpenoid or steroidal saponin plants, are often of interest for their therapeutic benefits in the treatment for conditions involving the Central Nervous System (CNS) e.g., Goji fruit (Lycium barbarum L.) that has been associated with improved cognitive function, [notably semantic fluency] 25. Herbal brain tonic Centella asciatica (L.) Urb. and Astragali membranaceus (Fisch. ex. Bunge.) contain their combination with an abundance of polysaccharides, amino acids, and flavonoids. Gynostemma pentaphyllum (Thunb.) Makino, and Polygalae tenuifolia Willd., [as well as having indications for cognitive impairments], have also included positive associations with insomnia, fatigue, depression and anxiety-related conditions. Generally, these are known to have a poor bioavailability, making it likely that they exert their effects through direct microbiota interaction 26, 27.

So., it might be said that modulating the microbiota, certainly appears to be very closely associated with many of the well-documented herbal medicines, that are commonly indicated specifically for their cognitive properties. And it is perhaps of no surprise then., that the noted cognitive-enhancing triterpenoid plant groups, also possess a number of other biological activities that may be supportive for our gut-environment…, typically these groups are anti-inflammatory, anti-allergic, and anti-microbial 28, 29.

Panax ginseng C.A. Mey. has its own specific triterpenoid saponins (ginsenosides), and forms perhaps the most well-known amongst the nervous system, brain and cognitive-support herbs. Their actions and prebiotic-like effects, have also been associated with biotransformation by Bifidobacterium, Bacteroides, and Eubacterium 30. However, ginsenoside benefits to mental health have also demonstrated potential involvements through many other pathways, including with the production of anti-inflammatory cytokines, neurotransmitter regulation (GABA, Dopamine, 5HT), glutamatergic systems, BDNF, and the HPA. Therefore, they have yet to be identified, as completely mediated through the gut-microbiome interaction pathway 31, 32.  

Terpenoid compounds [along with verbascoside], are main constituent of sleep-promoting Lemon Verbena (Aloysia citrodora Paláu), the essential oil of which has shown some further potential to reduce dysbiosis, also thought to be attributed to the flavonoids and polyphenols 33.

Many of our favourite botanical gut healers are potent in their oil forms. Peppermint Oil (Mentha × piperita L.) is known to be of amongst most frequent use for alleviating GIT pain, and related conditions34.

The volatile, biologically active oil of Lavender (Lavandula angustifolia Mill.) [monoterpenes, sesquiterpenes, and their oxygen derivatives], also frequently an herbal application for both gastrointestinal disorders as well as sleep conditions and anxiety, has unsurprisingly shown to exert antibacterial, antioxidant, analgesic, anti-inflammatory, anxiolytic, sedative, hypnotic, analgesic, and anticonvulsant with potential as antidepressant effects 35, 36, 37, 38. Oils of similar acting herbs that also display neuroendocrine and neurotrophic effects such as Bitter Orange (Citrus × aurantium L.), contain largely limonene and linalool, and have been shown to exert inhibitory effects on only harmful pathogens, whilst selectively having little or no effects, on the beneficial microbes 39.

However, in general, plants that contain volatile oils may technically be encouraged to interact with the microbiota, depending on other polar constituents such as polysaccharides that are present, rather than the essential oil itself. This is likely to be due to the fact that a low molecular weight of the oils’ constituents, may make them more easily absorbed at the upper intestine rather than interacting directly with microbiota, therefore it is likely that pathways other than the gut-brain, are responsible for its sleep-inducing effects40.

So., can we really improve our sleep and some of the related factors that are most likely to keep us awake at night., by targeting our gut health through pre., pro., and post., or phytobiotics?

Accumulating evidence indicates that the gut microbiota plays a significant role in the herbal treatment of sleep disorders and related conditions.

Polyphenols (e.g. berberine, resveratrol, curcumin, quercetin, gallate…,) have been studied intensely in their health benefits to provide support for the permeability and integrity of the gut barrier. Various multi-pathway herbs provide various functions for the gut-brain environment and connection (Glycyrrhiza glabra L. (Liquorice plant), Althaea officinalis L. (Marshmallow plant), Hibiscus sabdariffa L.41, 42, 43.

Gut microbiota are able to metabolise plant polysaccharides that are otherwise not digested in the upper gastro-intestinal tract. They are shown to be able to improve the overall balance of the microbial community and exert their effects through producing phenolic metabolites or postbiotic SCFA’s. These influence the gut through multiple pathways 44. Through mucus protection they are able to restore tight junctions in the leaky intestinal epithelium. Through a humoral pathway they can promote the synthesis of the neuropeptides and neurotropic factors. They are able to reduce neuroinflammatory activity or inflammatory mediators 45. Or., via neuronal pathway, SCFA’s may reduce cortisol. Medicinal herbs may form a critical part of the interactions that take place between the microbiota and the brain, and may be significantly related to the emotional and neurological components that promote wellbeing, and a more restorative, better-quality sleep.

References

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Botanical Information: World Flora Online (WFO) http://www.worldfloraonline.org/ November 2023 and POWO (2026). “Plants of the World Online. Facilitated by the Royal Botanic Gardens, Kew. Published on the Internet; https://powo.science.kew.org/.

Originally published: 12/12/2023
This article was recently reviewed by author for accuracy and updated on 5th October 2026, to include the latest information and taxonomy.

Whilst every care is taken to ensure accurate, reputable and the most recent sources and research for this information, this content is not intended as substitute for advice or treatment from a professional clinician. As with conventional medicines, herbal and natural medicines have active ingredients and can have potent effects and interactions with the body, medications, and with other conditions. Especially for those who are taking prescription or over-the-counter medications, it is advised to consult a professional herbalist or medical doctor before beginning any herbal, supplement or lifestyle program. Care and responsible administration is always strongly advocated.

Apothēcary of Botanical Medicine

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