Medicinal Plants and the Gut: How Herbs Influence the Microbiome

My starting point

With herbs, we almost always ask: what reaches the blood? Perhaps the more interesting question is: What happens along the way?

Does this sound familiar? You have turmeric capsules in the cupboard. Ginger in your tea. Maybe a bitter liqueur after meals, because your grandmother swore by it.

And at some point you read that curcumin is barely measurable in the blood. Then you rightly ask yourself: what's the point?

I love this question. Because it opens a door that classic herbal advice rarely opens. The gut is not just a pipe through which active compounds slip into the blood. It is an organ in its own right, with trillions of residents. And that is exactly where herbs arrive first.

In this article I show you an explanatory model from the perspective of KPNI, Clinical Psychoneuroimmunology. The core idea: many herbs might develop part of their effects via the microbiome and the intestinal barrier, rather than mainly via the blood. This is a hypothesis. I clearly separate what is established from what remains open.

Clinical study in humans Observation in humans Animal study Cell culture

The turmeric paradox: why so little reaches the blood

Imagine sending a letter across the country. Along the way it gets opened, rewritten and mostly thrown away. The recipient receives a scrap. That is roughly what happens to curcumin, the best-known compound from turmeric root.

Review · Anand 2007

In 2007, Anand and colleagues compiled what was known about the bioavailability of curcumin. Early clinical studies showed that curcumin was well tolerated even in high amounts of up to 12 grams a day. Nevertheless, levels in blood and tissue remained low, due to poor absorption, rapid metabolism and rapid elimination.

For you this means: the many laboratory findings on curcumin do not easily match what actually reaches the body systemically.

Anand P et al. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807-18.

This is exactly where an interesting line of thought begins. An Italian research group led by Scazzocchio brought together the research on curcumin and gut bacteria in 2020. The authors describe a contradiction: well-documented effects in the lab, but low bioavailability. Their hypothesis is that curcumin might act mainly in the gastrointestinal tract, where high concentrations were measured after ingestion.

A change of perspective

Low bioavailability does not automatically mean "ineffective". It could also mean: the most important site of action may lie before the bloodstream. A compound that stays in the gut can come into contact with bacteria and mucosal cells there. Whether this is clinically meaningful in humans remains to be seen.

And now you know why "barely reaches the blood" need not be the end of the story.

The gut axis model: how a herb might have effects by a detour

Perhaps you have noticed that your stomach reacts to stress. Or that your skin gets worse when your digestion acts up. That is no coincidence. The gut communicates with almost every system in your body.

From a KPNI perspective, a plant compound might take this route:

Arrival in the gut

A large share of many plant compounds is not absorbed in the small intestine and reaches the colon.

Transformation by bacteria

Gut bacteria can convert the molecules into smaller compounds, some of which are more easily absorbed. Like a kitchen that turns raw ingredients into a new dish.

Changing the residents

At the same time, plant compounds can influence which bacterial groups grow and which recede.

Intestinal barrier

The mucosa is like a border fence with doormen. Plant compounds might influence how tightly this fence holds and how many bacterial components get into the blood.

Effects throughout the body

Via immune messengers, bile acids and metabolic products, these local changes might affect inflammation, blood sugar and the nervous system.

Several reviews describe this interaction as running in both directions. As early as 2013, Cardona and colleagues emphasized that gut bacteria play a major role in the formation and bioavailability of polyphenol metabolites. But they also wrote that only a few studies had directly examined the effects on the human microbiome.

Curcumin and the mucosal border fence

Cell culture · Wang 2017

In 2017, Wang and colleagues studied human intestinal cell lines that were stimulated with lipopolysaccharide (LPS), a component of bacterial cell walls. Pretreatment with curcumin dampened the release of the inflammatory messenger IL-1β and slowed signaling pathways that loosen the connections between cells. The authors concluded that the intestinal cells and the barrier might be the most important site of action of curcumin, despite its low bioavailability.

For you this means: a plausible mechanism, measured in cell culture. It has not yet been confirmed in this form in humans.

Wang J et al. Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. Am J Physiol Cell Physiol. 2017;312(4):C438-C445.

Imagine the connections between intestinal cells as a zipper. When it opens, bacterial components such as LPS can enter the body more easily. The immune system sounds the alarm, often quietly and persistently. This silent inflammation is associated with metabolic disorders.

Curcumin and the human microbiome

RCT, pilot study · Peterson 2018

Peterson and colleagues gave 14 healthy people turmeric with piperine, curcumin with piperine, or placebo. In the placebo group, the number of detected bacterial species fell by an average of 15 percent; under curcumin it rose by an average of 69 percent. Above all, however, people responded very differently: there were responders and non-responders.

For you this means: turmeric might change the microbiome, but in a very individual way. A study with 14 people is a first clue, not proof.

Peterson CT et al. Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. J Evid Based Integr Med. 2018;23:2515690X18790725.

What this changes for you

If herbs work via your microbiome, then your reaction is not your neighbor's reaction. Two people, the same capsule, two different gut kitchens. That could explain why personal experiences with herbs vary so widely.

And now you know why the same plant can land differently in you than in others.

Polyphenols: food and signal for your gut bacteria

Think of colorful berries, cocoa, pomegranate, herbs and spices. They all contain polyphenols. These are large, often bulky molecules. For the small intestine they are hard to digest. For some bacteria in the colon they are a feast.

In 2019, Tomás-Barberán and Espín evaluated studies on citrus flavanones, pomegranate ellagitannins and cocoa proanthocyanidins. Their finding: the interaction between polyphenols and the microbiome could be relevant for explaining their health effects. The food matrix and processing also seem to play a role. However, the authors name clear research gaps before robust conclusions can be drawn.

Animal study · Anhê 2015

Anhê and colleagues fed mice a high-fat, high-sugar diet and gave some of them a polyphenol-rich cranberry extract in addition. The treated animals gained less weight, had better insulin sensitivity and less intestinal inflammation. At the same time, the proportion of Akkermansia rose markedly, a bacterium that lives in the mucus layer of the gut.

For you this means: an exciting association in a mouse model. Whether polyphenols can act the same way via Akkermansia in humans has not been conclusively clarified.

Anhê FF et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64(6):872-83.

Immune system

A large share of your immune cells sits around the intestinal mucosa. Less LPS in the blood could mean less constant irritation of these guards.

Metabolism

Bacterial metabolites and bile acids may be linked to insulin action and fat metabolism.

Nervous system

The gut has its own nerve network. Signals from the mucosa can travel toward the brain via the vagus nerve.

Hormonal system

Intestinal cells release hormones such as ghrelin or GLP-1. Plant compounds might trigger these signals via receptors in the gut.

And now you know why a colorful, plant-rich diet could be more than a source of vitamins from a microbiome perspective.

Ginger: what a placebo-controlled study has shown

You may know ginger as a remedy for nausea. It is often claimed that it also changes the gut flora. For a long time, human data on this were lacking.

RCT · Crichton 2023

An Australian research group led by Crichton gave 51 healthy young adults 1.2 grams of ginger root powder per day or placebo for 14 days. With ginger, the proportion of Actinobacteria rose more, individual genera increased, and Blautia decreased. Digestive symptoms improved somewhat, but overall microbiome diversity, bowel movements, mood and quality of life remained unchanged.

For you this means: ginger can shift individual bacterial groups. This short study in healthy people did not show major changes in wellbeing.

Crichton M et al. Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial. J Nutr. 2023;153(11):3193-3206.

An honest assessment

A change in the microbiome is not yet a noticeable benefit. Measurable is not the same as feelable. This distinction protects you from inflated expectations of any herb.

And now you know why I stay curious about ginger but make no big promises.

Bitter compounds: a taste that continues in the gut

Gentian, wormwood, dandelion, artichoke. Many cultures drink something bitter before or after a meal. It used to be said that this stimulates digestion. Today we know: bitter receptors are not only found on the tongue.

Animal study · Janssen 2011

Janssen and colleagues from Leuven studied bitter receptors in the stomach of mice. Bitter compounds given directly into the stomach increased the hunger hormone ghrelin. The animals ate briefly more in the first half hour, then less over several hours, and gastric emptying slowed.

For you this means: bitter compounds might influence hormones and stomach movement via receptors in the digestive tract. This has not yet been shown in this form in humans.

Janssen S et al. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 2011;108(5):2094-9.

This is a nice example of the core idea of this article. A bitter compound does not have to enter the blood to send a signal. It rings the doorbell of the intestinal cells, so to speak, and they pass the message on via hormones and nerves.

And now you know why an old kitchen custom might at least have a plausible biological basis.

Berberine: blood sugar via a bacterial detour?

Berberine comes from plants such as barberry. Online it is often marketed as "natural metformin". Labels like that make me cautious. All the more interesting to me is a large study that looked more closely.

RCT · Zhang 2020

At 20 centers in China, Zhang and colleagues treated 409 people with newly diagnosed type 2 diabetes for twelve weeks with berberine, probiotics, both, or placebo. Long-term blood sugar (HbA1c) fell by 0.99 percentage points with berberine alone and by 0.59 percentage points with placebo. The analysis suggested that the effect might be mediated by inhibition of bile acid conversion by the gut bacterium Ruminococcus bromii.

For you this means: a human clue that a plant compound can influence metabolic values via gut bacteria. However, berberine caused more gastrointestinal side effects.

Zhang Y et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020;11(1):5015.

Berberine is not a harmless kitchen herb. A compound that can measurably change bacteria and metabolism can also come into conflict with medications.

And now you know why "natural" does not mean the same as "free of side effects".

Peppermint oil: when the site of action is the gut itself

A cramping belly, bloating, the feeling that your gut does whatever it wants. If you know irritable bowel syndrome, you also know the helplessness. Peppermint oil is among the best-studied plant remedies in this area. It appears to act mainly locally on the intestinal muscles.

Meta-analysis · Alammar 2019

Alammar and colleagues evaluated twelve randomized studies with 835 people with IBS. Peppermint oil improved global symptoms and abdominal pain more often than placebo. Mathematically, three people had to be treated for one additional person to experience an improvement in overall symptoms; for abdominal pain it was four.

Alammar N et al. The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis of the pooled clinical data. BMC Complement Altern Med. 2019;19(1):21.

Meta-analysis · Ingrosso 2022

An updated analysis by Ingrosso and colleagues pooled ten randomized studies with 1030 people. Peppermint oil performed better than placebo for overall symptoms and abdominal pain. However, side effects occurred more often, and the quality of the evidence was rated as very low.

For you this means: peppermint oil can be a reasonable option for IBS, but the data are less solid than they seem at first glance. Larger studies are lacking.

Ingrosso MR et al. Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome. Aliment Pharmacol Ther. 2022;56(6):932-941.

And now you know why I place two meta-analyses side by side: the numbers can shift with new studies.

What is established, what is hypothesis?

Maybe you now feel like reorganizing your herb cupboard. Before you do, let's separate things honestly.

Well established

Curcumin has low oral bioavailability.
Peppermint oil shows benefits for IBS in meta-analyses, with limitations.
Gut bacteria transform polyphenols.

Plausible, thin human data

Curcumin might strengthen the intestinal barrier.
Turmeric and ginger change individual bacterial groups.
Berberine might influence blood sugar partly via bacteria.

Still open

Whether the microbiome axis is the main pathway of plant effects.
Who responds to which herb.
Which effects are noticeable in the long term.

"To me, the gut axis is not proof, but a good map. It helps us ask better questions."

For me, there is also a piece of freedom in this. When you understand that your gut has a say, you are no longer a consumer of miracle capsules. You become the host of a living ecosystem. That is bigger than a single symptom. It is about how you feel in your body over the long term.

Safety: what you should know before taking herbal supplements

Herbs in the kitchen are something different from highly concentrated extracts in capsules. Two studies show this particularly clearly.

Case reports · Lombardi 2021

Lombardi and colleagues described seven cases of acute liver inflammation in Tuscany after turmeric dietary supplements and evaluated 23 further published cases. The Tuscan cases involved formulations with high bioavailability and a high curcuminoid dose. Most of those affected recovered after stopping, and many were also taking other medications.

For you this means: liver damage is rare, but it does occur. And it seems to occur particularly with the products designed to get as much curcumin as possible into the blood.

Lombardi N et al. Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2021;87(3):741-753.

A thought worth pondering

If curcumin develops part of its effects in the gut, then the race for ever higher bioavailability could be a double-edged sword. More in the blood does not necessarily mean more benefit, but possibly more strain on the liver. This is a hypothesis, not a recommendation.

RCT, crossover · Guo 2012

Guo and colleagues gave healthy men berberine for two weeks, 300 milligrams three times a day. Afterwards, the activity of the liver enzymes CYP2D6, CYP2C9 and CYP3A4 was inhibited. Blood levels of the test drug midazolam were around 40 percent higher.

For you this means: berberine can slow the breakdown of other medications. The authors advise taking interactions into account.

Guo Y et al. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7.

Please be especially careful

Long-term medications: If you take anticoagulants, blood sugar lowering drugs, antidepressants or other regular medications, discuss every concentrated plant supplement with a physician beforehand.
Liver: With turmeric extracts, especially highly bioavailable ones, watch for warning signs such as dark urine, yellowish skin or persistent upper abdominal discomfort, and have them checked by a physician right away.
Pregnancy and breastfeeding: Sufficient safety data are lacking for concentrated extracts such as berberine or high-dose curcumin. Do not take anything on your own here.
A spice is not a capsule: Turmeric, ginger and herbs in usual kitchen amounts are something different from high-dose extracts.

And now you know why I ask about plant supplements just as carefully as about medications.

Three levers you can start with today

You don't have to understand everything to get started. These three steps fit into everyday life and need no supplements.

Variety instead of a single herb

Over the week, bring as many different plants as possible onto your plate: herbs, spices, berries, bitter salads such as radicchio or arugula. Your microbiome might benefit more from variety than from a single high-dose capsule.

Observe instead of guessing

When you introduce a new herb, note your digestion, energy and sleep for two to three weeks. The studies show very individual reactions. Your own notes show you whether you are more likely a responder.

Bring your medication list

Before you start a concentrated supplement, write down all medications and dietary supplements and have them reviewed by a physician. It takes five minutes and can protect you from interactions.

Frequently asked questions about medicinal plants, the gut and the microbiome

How do medicinal plants reach the gut, and what happens to them there?

Many plant compounds are only partly absorbed in the small intestine. A large share reaches the colon. There, gut bacteria can transform the molecules, and in turn the plant compounds can change the composition of the bacteria. Reviews describe this as a two-way interaction.

Why does so little curcumin reach the blood?

According to a review by Anand and colleagues from 2007, the reasons are poor absorption, rapid metabolism and rapid elimination. Even high amounts lead only to low levels in blood and tissue.

Can turmeric have effects despite its low bioavailability?

That is an open question. One hypothesis is that curcumin acts mainly where it is present in high concentration: in the gut. Cell studies show effects on the intestinal barrier, and a small pilot study showed changes in the microbiome. This explanatory model has not yet been confirmed in humans.

Does ginger change the gut flora in humans?

In a placebo-controlled study with 51 young healthy adults, ginger powder changed individual bacterial groups over 14 days. Microbiome diversity, bowel habits and mood did not change. Symptoms of indigestion improved somewhat.

What do bitter compounds have to do with the gut?

Bitter receptors are found not only on the tongue but also in the stomach and intestine. In a study in mice, bitter compounds released the hunger hormone ghrelin and slowed gastric emptying. Whether this translates directly to humans remains open.

Does berberine influence blood sugar via the microbiome?

In a randomized study with 409 people with newly diagnosed type 2 diabetes, berberine lowered HbA1c more than placebo. The analysis suggests that part of the effect might run through gut bacteria and bile acids. Berberine caused more gastrointestinal side effects and can inhibit liver enzymes that break down medications.

Is peppermint oil useful for irritable bowel syndrome?

Two meta-analyses found that peppermint oil may improve global IBS symptoms and abdominal pain compared with placebo. However, the newer analysis from 2022 rates the quality of the evidence as very low and found more side effects. Peppermint oil appears to act mainly locally on the intestinal muscles.

Are turmeric supplements dangerous for the liver?

Rarely, yes. Italian case reports describe acute liver inflammation after turmeric dietary supplements, mostly with highly bioavailable and high-dose formulations. Most cases improved after stopping the supplement. The spice used in cooking is a different matter.

What should I watch out for with herbal supplements and medications?

Concentrated plant extracts can interact with medications. In a study in healthy men, berberine inhibited several liver enzymes that break down drugs. If you take anticoagulants, blood sugar medications or other long-term medications, discuss every supplement with a physician beforehand. This applies especially during pregnancy and breastfeeding.

Should I have my microbiome tested before taking herbs?

A stool test can provide clues, but it does not yet predict how you will respond to a particular herb. The turmeric pilot study showed very individual responses, with responders and non-responders. Placing your symptoms in the overall picture is often more useful than a test alone.

Sources

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807-18. DOI: 10.1021/mp700113r [Review]
Scazzocchio B, Minghetti L, D'Archivio M. Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin. Nutrients. 2020;12(9):2499. DOI: 10.3390/nu12092499 [Review]
Wang J, Ghosh SS, Ghosh S. Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. Am J Physiol Cell Physiol. 2017;312(4):C438-C445. DOI: 10.1152/ajpcell.00235.2016 [In vitro, human intestinal epithelial cell lines]
Peterson CT, Vaughn AR, Sharma V et al. Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. J Evid Based Integr Med. 2018;23:2515690X18790725. DOI: 10.1177/2515690X18790725 [RCT, pilot study, n=14]
Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24(8):1415-22. DOI: 10.1016/j.jnutbio.2013.05.001 [Review]
Tomás-Barberán FA, Espín JC. Effect of Food Structure and Processing on (Poly)phenol-Gut Microbiota Interactions and the Effects on Human Health. Annu Rev Food Sci Technol. 2019;10:221-238. DOI: 10.1146/annurev-food-032818-121615 [Review]
Anhê FF, Roy D, Pilon G et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64(6):872-83. DOI: 10.1136/gutjnl-2014-307142 [In vivo, mouse]
Crichton M, Marshall S, Marx W et al. Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial. J Nutr. 2023;153(11):3193-3206. DOI: 10.1016/j.tjnut.2023.09.002 [RCT, n=51, healthy adults]
Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 2011;108(5):2094-9. DOI: 10.1073/pnas.1011508108 [In vivo, mouse]
Zhang Y, Gu Y, Ren H et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020;11(1):5015. DOI: 10.1038/s41467-020-18414-8 [RCT, n=409, type 2 diabetes]
Alammar N, Wang L, Saberi B et al. The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis of the pooled clinical data. BMC Complement Altern Med. 2019;19(1):21. DOI: 10.1186/s12906-018-2409-0 [Meta-analysis, 12 RCTs, n=835]
Ingrosso MR, Ianiro G, Nee J et al. Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome. Aliment Pharmacol Ther. 2022;56(6):932-941. DOI: 10.1111/apt.17179 [Meta-analysis, 10 RCTs, n=1030]
Lombardi N, Crescioli G, Maggini V et al. Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2021;87(3):741-753. DOI: 10.1111/bcp.14460 [Systematic Review, case reports]
Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. 2012;68(2):213-7. DOI: 10.1007/s00228-011-1108-2 [RCT, crossover, healthy men]

The core idea of this article, that medicinal plants might develop part of their effects via the microbiome and the intestinal barrier, is an explanatory model. So far, few large human studies exist on this topic. The associations presented here are based in part on physiological principles, mechanistic studies in human cells and animal models. This is biologically plausible, but not yet established with the same certainty as large randomized studies would provide. This article does not replace medical advice.