Effects of a 6-months Fiber- and Polyphenol-rich Diet on Brain Inflammatory Processes in Perimenopausal Women Living With Overweight or Obesity (INFLAME)

Effects of a Fiber- and Polyphenol-rich Diet on Brain Inflammatory Processes in Obesity

People living with obesity have a higher risk of late-life cognitive decline and developing dementia. In women, the risk of cognitive decline may further raise during the menopausal transition, a period of substantial hormonal and metabolic changes.

Recent studies suggest that a healthy diet could help to prevent neurocognitive disorders by reducing inflammatory processes in the body and brain. Emerging evidence further indicates that the gut-brain axis and the intestinal microbiome play a crucial role in mediating this effect, through metabolic, immune, neuronal and vascular routes. Modifying the gut microbiota may thus counteract the heightened systemic inflammation seen in obesity and during menopausal transition to eventually benefit brain health.

Specifically, plant-based nutirents, such as fibre and polyphenols, have microbiome-changing, anti-inflammatory and neuroprotective properties that may slow brain aging and neuro-inflammation. However, evidence from human interventional studies and knowledge on the underlying mechanisms remain scarce.

This randomized controlled trial will therefore test whether altering gut bacteria through six months of daily intake of a personalized "polybiotic" dietary formula, compared to placebo, improves markers of brain health in women during the perimenopausal transition that are living with overweight or obesity. We plan to enroll 120 women aged 35-60 with overweight/obesity and elevated inflammatory blood markers, randomized to: intervention (7.5 or 15 g inulin, plus 200 mg resveratrol and 320 mg quercetin per day in powder form with main meals) or control (isocaloric maltodextrin). Exclusions include type 1 diabetes, current psychiatric/gastrointestinal disorders, and magentic resonance imaging (MRI) contraindications.

Before and after 26 weeks, participants will undergo brain MRI to assess inflammation-related brain markers, neuropsychological testing, anthropometric measurements, they will fill in a set of questionnaires and donate stool and blood. Gut bacteria will be profiled by next-generation sequencing; metabolites will be measured in blood and stool. The primary outcome is a proxy of neuroinflammation in the white matter assessed using diffusion-weighted MRI. Secondary analyses will examine blood-brain-barrier permeability and other functional and structural MRI measures, including MR spectoscropy. Mechanistic links among changes in inflammatory markers, microbiota composition, and short-chain fatty acids will be explored using path and network models.

This study may help to develop novel prevention and treatment strategies to mitigate obesity-related cognitive decline via the gut-brain axis.

Study Overview

• Status: Recruiting
• Conditions: Overweight and/or Obesity; Perimenopausal Women
• Intervention / Treatment: Dietary supplement: Polybiotic dietary intervention; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Recruiting
      • Max Planck Institute for Human Cognitive and Brain Sciences
      • Contact: Omegalab; Phone Number: +49 341 9940-2417; Email: in-flame@cbs.mpg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• STRAW+10 -1 or -2
• BMI > 25 or WHR >= 0.85
• hsCRP > 1 mg/l
• no MRI contra-indication
• written informed consent

Exclusion Criteria:

• occurrence of a clinically relevant psychiatric disease in the last 12 months (e.g., depression, substance abuse, eating disorder, schizophrenia)
• type 1 diabetes
• previous bariatric/gastric surgery
• pregnancy or breastfeeding woman
• severe untreated disease, cancer treatment last 12 months, any chronic gastric tract disease (IBS, Morbus Crohn, Heliobacter pylori Infection etc.) or any chronic inflammatory disease
• Polycystic ovary syndrome, total ovarectomy
• Intake of antibiotics in past 3 months, intake of inulin (>5g/day) or polyphenol supplementation (>50mg/day) in past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized intervention arm; Daily intake of 7.5g or 15g of inulin + 200mg resveratrol + 320mg quercetin in a powder formula with main meals in the first half of day, over the course of 6 months. The lower or higher inulin dosage will be assigned depending on the participants' microbiome composition at baseline.	Dietary supplement: Polybiotic dietary intervention; 7.5g or 15g of inulin + 200mg resveratrol + 320mg quercetin in a powder formula
Placebo Comparator: Placebo arm; Daily intake of equicaloric maltodextrin	Dietary supplement: Placebo; Equicaloric maltodextrin in powder form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free water fraction averaged across the white matter skeleton	Free water (measured using multi-shell diffusion-weighted MRI at 3 Tesla) reflects extra-cellular water which can be considered an indicator of tissue edema and impaired blood brain barrier	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average grey matter kw from motion-compensated diffusion-weighted arterial spin labeling (ASL)	Water exchange rate over the blood-brain barrier will be measured using motion-compensated diffusion-weighted pseudo-continuous arterial-spin labeling (MCDW-ASL) or diffusion-prepared pCASL (DP-pCASL).	6 months
Apparent diffusion coefficient of metabolites in the thalamus from diffusion-weighted MR spectoscropy	microglial activity will be quantified by measuring ADCCholine using diffusion-weighted magnetic resonance spectroscopy (dwMRS)	6 months
Hypothalamic and hippocampal microstructure	microstructure will be assessed by mean diffusivity (MD)	6 months
Episodic memory	California Verbal Learning Task	6 months
Microbial Composition	Alpha/Beta diversity and abundance of specific bacteria (e.g. bifidobacteria) from microbiome shotgun sequencing	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
soma signal fraction in thalamus and hippocampus derived from multi-shell diffusion-weighted MRI	assessed using multi-shell diffusion-weighted MRI at 3T	6 months
Pattern separation	Dprime and accuracy, reaction time of Mnemonic Similarity Task (MST)	6 months
Executive function	Composite score of executive function tests derived from Trail Making Test, Attention Network Test, Stroop-Test	6 months
pro-inflammatory marker high-sensitive C-reactive protein (hsCRP)	hsCRP measured in fasting blood	6 months
waist-to-hip ratio, WHR	ratio of waist circumeference to hip circumference (measured)	6 months
Adherence to healthy dietary pattern	A composite score based on self-reported information provided through diet protocol and food frequency questionnaire (FFQ)	6 months
Menopausal symptoms	severity of menopausal symptoms based on a questionnaire	6 months
Assessment of health data	via wearables - smart devices finger ring and/or watch and glucose patch	6 months (during 2 weeks at baseline, and follow-up, respectively)
Demographics, anamnesis	Age, sex/gender, medical history, reproductive history, medication	6 months
Total energy expenditure measured using a metabolic chamber	Oxygen consumption and CO2 production measured in a metabolic chamber, determining 24-hour total energy expenditure (TEE)	6 months
body fat percentage	measured using bioelectrical impedance analysis (BIA)	6 months
Gastrointestinal hormones	area under the curve (pre- to postprandial) of glukagon-like peptide 1 (GLP-1)	6 months
Sex hormones	Follicle-stimulating hormon (FSH) measured in blood	6 months

Collaborators and Investigators

• Sponsor: Max Planck Institute for Human Cognitive and Brain Sciences
• Investigators: Principal Investigator: Veronica Witte, PhD, University of Leipzig Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: obesity; overweight; prevention; cognitive decline; diet; gut-brain axis; MR spectroscopy; neuroinflammation; diffusion-weighted MRI; brain aging; menopausal transition; open science
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Nutrition Disorders; Overnutrition; Body Weight; Neurocognitive Disorders; Inflammation; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Neuroinflammatory Diseases; Overweight; Obesity; Cognitive Dysfunction
• Other Study ID Numbers: NRO-286

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No