Microbiome Modulation

1. What This Mechanism of Action Is

Gut microbiome modulation describes the targeted alteration of the microbial community in the gut. These microorganisms are involved in metabolic processes, immune regulation, and the production of bioactive metabolites. An altered composition can influence inflammatory processes, nutrient absorption, and even neurological functions. The interaction between the host organism and the microbiome is complex and is shaped by diet, medications, and environmental factors.

Measuring microbiome changes in humans is challenging due to high individual variability. Controlled studies require standardised conditions, large sample sizes, and long-term observations. Furthermore, not all microbial changes are clinically relevant. Laboratory and animal studies provide insights, but extrapolation to humans is not always possible.

2. Which Substances Are Associated with It

All substances in the database for which this mechanism of action is described — ranked by the extent of human testing. The numbers represent studies per type of investigation.

3. How Robust the Evidence Is

Probiotics have the strongest evidence base, with numerous controlled human studies. Omega-3 fatty acids, turmeric/curcumin, vitamin D, and beta-glucans also show effects on the gut microbiota in controlled trials. Substances such as humic acid complexes, quercetin, or black cumin, however, have scarcely been studied in humans. Laboratory and animal experiments suggest potential effects, but clinical data are lacking.

Many substances act through similar mechanisms, such as anti-inflammatory or direct antimicrobial effects. While extrapolating findings from laboratory or animal studies to humans is plausible, it is not conclusive. For example, humic acid complexes modulate the gut microbiota in animal studies, but corresponding human studies are absent. A similar situation applies to substances like sulforaphane or astaxanthin.

4. Key Human Studies

• 1 Endotoxins and Non-Alcoholic Fatty Liver Disease (2021) — Gut microbiome
• 2 Probiotic supplementation during antibiotic treatment is unjustified in maintaining the gut microbiome diversity: a systematic review and meta-analysis (2023) — Gut microbiome
• 3 Inulin-type fructans and 2'fucosyllactose alter both microbial composition and appear to alleviate stress-induced mood state in a working population (2023) — Gut microbiome
• 4 A randomised double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer (2019) — Probiotics
• 5 Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants (2018) — Probiotics
• 6 Probiotic supplementation in diabetic haemodialysis patients has beneficial metabolic effects (2017) — Probiotics
• 7 Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining (2022) — Chronic inflammation
• 8 The influence of an anti-inflammatory diet on gingivitis. A randomised controlled trial (2019) — Chronic inflammation
• 9 An anti-inflammatory and low fermentable oligo-, di-, and monosaccharides and polyols diet improved patient-reported outcomes in fibromyalgia: A randomised (2022) — Chronic inflammation
• 10 Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic (2020) — Omega-3 fatty acids
• 11 Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight (2023) — Omega-3 fatty acids
• 12 Effect of Plant-Derived n-3 Polyunsaturated Fatty Acids on Blood Lipids and Gut Microbiota: A Double-Blind Randomised Controlled Trial (2022) — Omega-3 fatty acids
• 13 Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study (2018) — Turmeric and Curcumin
• 14 Can curcumin supplementation disrupt the vicious cycle of inflammation, oxidative stress, and uraemia in patients undergoing peritoneal dialysis? (2024) — Turmeric and Curcumin
• 15 Effects of Dietary Components on Mast Cells: Potential Use as Nutraceuticals for Allergies? (2023) — Turmeric and Curcumin
• 16 Impact of high-dose cholecalciferol (vitamin D₃) and inulin prebiotic on intestinal and airway microbiota in adults with cystic fibrosis: A 2×2 randomised trial (2024) — Vitamin D
• 17 A clinical study on the effects of teriparatide and denosumab on bone metabolism and gut microbiota in patients with osteoporotic fractures (2026) — Vitamin D
• 18 Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomised, placebo-controlled, double-blind, 2×2 trial (2024) — Vitamin D
• 19 Fibre mixture-specific effect on distal colonic fermentation and metabolic health in lean but not in prediabetic men (2022) — Beta-Glucans
• 20 A randomised controlled trial of a probiotic and a prebiotic examining metabolic and mental health outcomes in adults with prediabetes (2022) — Beta-Glucans
• 21 The separate effects of whole oats and isolated beta-glucan on lipid profile: A systematic review and meta-analysis of randomised controlled trials (2023) — Beta-Glucans
• 22 Efficacy of (-)-epigallocatechin gallate delivered by a new-type scaler tip during scaling and root planing on chronic periodontitis: a split-mouth randomised controlled trial (2021) — Green Tea and EGCG
• 23 Green Tea Kombucha Impacts Inflammation and Salivary Microbiota in Individuals with Excess Body Weight: A Randomised Controlled Trial (2024) — Green Tea and EGCG
• 24 Green Tea Catechin Plus Inulin Improves Insulin Resistance Without Reducing Visceral Fat and Shows Exploratory Gut Microbiota Signals in Adults with Visceral Obesity (2026) — Green Tea and EGCG

5. Open Questions

• Humic acid complexes: Are there measurable effects on the human gut microbiota, and if so, under what conditions?
• Long-term effects: How stable are microbiome changes after discontinuation of the substances, and what is their clinical relevance?
• Individual variability: Which factors (genetics, diet, medication) influence the efficacy of microbiome-modulating substances?
• Combination therapies: Can substances such as probiotics and omega-3 fatty acids act synergistically, and how can this be demonstrated in humans?
• Specific bacterial strains: Which microorganisms are selectively promoted or inhibited by which substances, and what are the clinical consequences?

See also the gap list for all substances. This page is recalculated with each update.