Study finds indole treatment in pregnant mice improves offspring liver health and metabolism — Evidence Review
Published in eBioMedicine, by researchers from University of Oklahoma
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Table of Contents
A new study suggests that maternal supplementation with indole, a compound produced by gut bacteria, could help prevent fatty liver disease in offspring exposed to high-fat, high-sugar diets. Related research largely supports these findings, highlighting indole and its metabolites as protective against liver disease and metabolic dysfunction. Read more at the University of Oklahoma.
- Multiple studies show that indole and its derivatives, such as indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA), can reduce liver inflammation, improve fat metabolism, and lower blood sugar in animal models of fatty liver disease, aligning with the new study’s outcomes 1 2 3 4 5 11.
- Maternal diet and gut microbiota composition are increasingly recognized as influential in offspring metabolic health, with related work demonstrating that Western-style diets or altered maternal microbiomes can impair protective indole metabolite levels in offspring, increasing disease risk 7 8.
- Some research has explored maternal interventions, including probiotic or dietary supplementation, that boost indole compound production, suggesting early-life or prenatal strategies may be effective for disease prevention 8 9.
Study Overview and Key Findings
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common in children, particularly those whose mothers consume high-fat, high-sugar diets during pregnancy and breastfeeding. The new study examines whether this risk can be mitigated by targeting the maternal microbiome. By supplementing pregnant and nursing mice with indole—a compound naturally produced by gut bacteria from dietary tryptophan—the researchers investigated whether this intervention could protect offspring from developing MASLD, even when later exposed to a Western-style diet. The work is significant in its focus on preventive strategies and the potential for microbiome-derived compounds to impact intergenerational health.
| Property | Value |
|---|---|
| Study Year | 2026 |
| Organization | University of Oklahoma |
| Journal Name | eBioMedicine |
| Authors | Ashok Mandala, Ram Babu Undi, Rachel C. Janssen, Kameron Y. Sugino, Wanke Zhao, Benjamin N. Nelson, April M. Teague, Nikhil Y. Patil, Karin Zemsky Berry, Rohan Varshney, Bryan C. Bergman, Michael C. Rudolph, Aditya D. Joshi, Raju V.S. Rajala, Karen R. Jonscher, Jacob E. Friedman |
| Population | Pregnant and nursing mice and their offspring |
| Methods | Animal Study |
| Outcome | Metabolic health indicators in offspring, liver health |
| Results | Offspring of indole-treated mothers had healthier livers and lower blood sugar. |
Literature Review: Related Studies
To place this study in context, we searched the Consensus database, which includes over 200 million research papers. The following search queries were used to identify related studies:
- indole compound liver disease prevention
- maternal indole treatment offspring health
- blood sugar levels indole liver effects
Below, we summarize key themes and findings from the literature:
| Topic | Key Findings |
|---|---|
| How do indole and its metabolites affect liver disease development and progression? | - Indole and metabolites like IAA and IPA alleviate fatty liver disease, reduce hepatic inflammation, and improve metabolic markers in animal models 1 2 3 4 5 11. - Higher levels of indole compounds are associated with reduced liver fat and inflammation in both animals and humans 4 5 11. |
| What is the impact of maternal diet and microbiome on offspring liver and metabolic health? | - Maternal Western-style diets impair offspring microbiome composition, leading to reduced indole metabolites and increased MASLD risk 7. - Maternal intake of indole-producing foods or probiotics can transfer protective metabolites to offspring, improving gut and immune development 8 9. |
| Can early-life or prenatal interventions targeting indole pathways prevent disease? | - Maternal supplementation with indole or indole-producing probiotics during pregnancy/lactation increases protective microbiome metabolites in offspring, reducing disease susceptibility 8 9. - Transfer of healthy microbiota or indole compounds to offspring can confer long-term metabolic and immune benefits 8 9. |
How do indole and its metabolites affect liver disease development and progression?
The body of research strongly supports the protective effects of indole and its derivatives against liver disease. Multiple animal studies report that supplementation with indole compounds, including IAA and IPA, reduces hepatic steatosis, inflammation, and markers of metabolic dysfunction. There is also evidence that circulating indole levels in humans inversely correlate with liver fat content and obesity measures, suggesting relevance to human disease.
- Indole and its derivatives consistently reduce hepatic fat accumulation and inflammation in animal models of NAFLD and MASLD 1 2 3 4 5.
- Supplementation with IAA or IPA improves insulin sensitivity, lipid metabolism, and lowers oxidative and inflammatory stress in the liver 1 2 5 11.
- Indole compounds act through various mechanisms, including modulation of gut barrier integrity, suppression of inflammatory pathways (such as NF-κB), and regulation of key metabolic genes 2 3 4 5 11.
- Human studies indicate lower circulating indole levels in obese individuals and those with higher liver fat, suggesting a potential biomarker or therapeutic target 4 5 11.
What is the impact of maternal diet and microbiome on offspring liver and metabolic health?
Emerging evidence highlights the crucial role of maternal microbiome and diet in shaping offspring health outcomes. Maternal consumption of a Western-style diet induces dysbiosis in offspring, resulting in reduced levels of protective indole metabolites and increased risk for metabolic diseases, including MASLD. Conversely, maternal intake of indole-rich foods or probiotics can enhance neonatal immune and metabolic development.
- Maternal Western diet exposure leads to gut dysbiosis and lower indole levels in offspring, impairing aryl hydrocarbon receptor (AHR) signaling and innate immune responses 7.
- Transfer of altered maternal microbiota to offspring is sufficient to induce immune hypo-responsiveness and promote disease progression 7.
- Maternal consumption of fermented foods or probiotics that boost indole derivatives can enhance the development of gut immune cells in offspring 8.
- These findings support the rationale for maternal interventions aimed at restoring microbiome function and protective metabolite production 7 8.
Can early-life or prenatal interventions targeting indole pathways prevent disease?
Several studies suggest that early-life interventions, such as maternal supplementation with indole or administration of indole-producing bacteria or fermented foods, may offer lasting protection against metabolic and inflammatory diseases in offspring. These strategies appear to enhance the transfer of beneficial metabolites across the placenta or through milk, promoting healthy gut, immune, and metabolic development.
- Maternal intake of indole-rich yoghurt or probiotics during pregnancy increases indole metabolites in milk, boosting offspring gut immune cell development 8.
- Prenatal supplementation with IPA can cross the placenta, improve fetal gut development, and reduce later susceptibility to colitis and inflammation 9.
- Transfer of healthy maternal microbiota or indole compounds to offspring leads to improved gut barrier function and metabolic health 8 9.
- These results align with the new study’s findings, supporting the potential for preventive strategies during pregnancy and lactation 8 9.
Future Research Questions
While current evidence supports the protective effects of maternal indole supplementation on offspring metabolic health, further research is needed to clarify mechanisms, optimize interventions, and assess safety and efficacy in humans. The following questions highlight areas for future investigation:
| Research Question | Relevance |
|---|---|
| Does maternal indole supplementation prevent fatty liver disease in humans? | Most studies to date are in animal models; direct evidence in humans is lacking. Understanding translational potential is crucial for clinical application 4 5 11. |
| What are the optimal types and doses of indole compounds for preventing metabolic disease? | Different indole metabolites (IAA, IPA, etc.) may have varying effects, and safe, effective dose ranges need to be established for human use 1 2 3 4 5 11. |
| How does maternal microbiome composition influence indole production and offspring health? | The relationship between specific maternal gut microbes, indole production, and intergenerational health outcomes remains incompletely understood 7 8. |
| Are there long-term effects of early-life indole exposure on immune and metabolic health? | Some studies suggest lasting benefits for gut and immune development, but long-term safety and efficacy data are needed 8 9. |
| Can dietary or probiotic interventions effectively modulate maternal indole levels? | Understanding which dietary or probiotic strategies most reliably increase protective indole metabolites could inform preventive recommendations 8. |
This article presents a synthesis of the latest research on maternal indole supplementation and its role in offspring liver health, with links to further information and ongoing research questions.