MicrobiomeX® - Clinical Research Data Summary

MicrobiomeX® Citrus Flavobiotic®

MicrobiomeX® is a clinically studied ingredient used in the following Silver Fern™ Brand product:

Targeted Prebiotic – https://www.silverfernbrand.com/products/targeted-prebiotic

Introduction

MicrobiomeX® is a citrus-derived flavobiotic® composed of standardized citrus flavonoids designed to support gut microbiome activity and gut barrier function. Rather than adding bacteria, MicrobiomeX® works by supporting beneficial microbial activity — encouraging shifts in microbial metabolites such as short-chain fatty acids, including butyrate, which has been associated with gut barrier function and immune signaling. Backed by human clinical research at a low daily dose, MicrobiomeX® offers a targeted approach to supporting gut health, immune balance, and healthy inflammatory responses through microbiome modulation.*

These are the studies for MicrobiomeX®. Below, we provided a summary of each key data for each study, along with a link to the complete clinical research.

Ingredient Manufacturer Website: https://microbiomex.com/

Study 1 Summary

Complete Study Information: https://www.researchgate.net/publication/373944066_Citrus_Extract_High_in_Flavonoids_Beneficially_Alters_Intestinal_Metabolic_Responses_in_Subjects_with_Features_of_Metabolic_Syndrome

Citrus Extract High in Flavonoids Beneficially Alters Intestinal Metabolic Responses in Subjects with Features of Metabolic Syndrome
Maurer Sost, M., van Hul, M., et al. Foods. 2023;12(18):3397.

This human clinical study evaluated the effects of daily supplementation with 500 mg of a citrus flavonoid extract for 12 weeks on gut microbial metabolic activity in adults with features of metabolic syndrome. The study also included a validated in vitro colon model (TIM-2) providing mechanistic support for the observed findings.

Study Design Highlights

Human clinical supplementation: 500 mg/day citrus flavonoid extract, 12 weeks, adults with features of metabolic syndrome
In vitro colon model: TIM-2 system, 72-hour continuous exposure equivalent to 500 mg/day
Primary outcomes: Fecal SCFA profile, fecal calprotectin

Key Findings (What the Study Showed)

1. Shift in Short-Chain Fatty Acid (SCFA) Profile

Butyrate / total SCFA ratio: 0.18 → 0.19 (approximately +6% relative increase)
Statistically significant vs. placebo (p = 0.022)
Butyrate is a short-chain fatty acid commonly associated with gut barrier integrity, balanced immune signaling, and gut-derived metabolic signaling pathways

2. Absolute Butyrate Levels (Trend)

Butyrate concentration: 12.4 → 15.0 µmol/g feces (approximately +21% increase)
Directionally consistent with the observed SCFA composition shift, though not statistically significant (p = 0.249)
Suggests the relative pattern of microbial fermentation changed even though total SCFA concentrations remained similar

3. Fecal Calprotectin (Exploratory Biomarker)

Estimated approximately 20–25% reduction vs. placebo (based on study figure)
Statistical trend toward significance (p = 0.058)
Calprotectin is a biomarker commonly used to assess intestinal immune activity

4. In Vitro Colon Model (TIM-2) — Mechanistic Support

After 72 hours of continuous exposure equivalent to 500 mg/day:

Total SCFAs: 193.3 → 201.7 mmol (~+4.3%)
Butyrate: 53.4 → 61.2 mmol (~+14.6%)
Valerate: 2.8 → 4.2 mmol (~+50%)
Branched-chain fatty acids: 7.3 → 4.0 mmol (~−45%)

These changes suggest a shift in microbial fermentation patterns toward greater carbohydrate fermentation relative to protein fermentation in the colon model.

What Did Not Change

Body weight, BMI, and total fecal SCFA concentration were unchanged — consistent with the study design focused on microbial metabolic activity rather than weight loss

Benefits of MicrobiomeX® Demonstrated by This Study

Based directly on the clinical and model findings, MicrobiomeX® was shown to:
✓ Support a statistically significant shift in butyrate proportion among SCFAs
✓ Support a directional increase in absolute butyrate levels (+21%)
✓ Show a trend toward lower fecal calprotectin, a gut immune activity marker
✓ Support a shift toward carbohydrate vs. protein fermentation patterns in a validated colon model
✓ Demonstrate butyrate-promoting effects at a low daily dose of 500 mg

Why This Study Matters

Daily supplementation with 500 mg of a citrus flavonoid extract for 12 weeks was associated with shifts in gut microbial metabolic activity in adults with features of metabolic syndrome, including an increased relative proportion of butyrate among short-chain fatty acids. A trend toward lower fecal calprotectin was also observed. Together with findings from the validated colon model, these results suggest citrus flavonoids may influence microbial fermentation patterns and support pathways associated with gut barrier integrity and immune signaling.*

Reference Link: https://www.researchgate.net/publication/373944066

Study 2 Summary

Complete Study Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619629/

A Citrus Fruit Extract High in Polyphenols Beneficially Modulates the Gut Microbiota of Healthy Human Volunteers in a Validated In Vitro Model of the Colon
Van Hul, M., et al. Nutrients. 2021;13(11):3915.

This study evaluated how citrus flavonoid extract influences gut microbiota composition and fermentation metabolites using a validated in vitro human colon simulation model inoculated with fecal microbiota from healthy human volunteers.

Study Design Highlights

Study type: Validated in vitro human colon simulation model
Inoculum: Fecal microbiota from healthy human volunteers
Doses tested: 250 mg/day and 350 mg/day equivalents
Comparison: Citrus extract vs. control conditions
Duration: 72-hour fermentation window

Key Findings (What the Study Showed)

1. Key Microbiome Changes

Compared with control conditions, citrus extract increased the relative abundance of several microbial taxa associated with polyphenol metabolism and short-chain fatty acid production, including:

Roseburia (butyrate-producing genus)
Eubacterium ramulus (polyphenol-metabolizing species)
Bacteroides eggerthii (polyphenol-associated metabolite producer)
Limosilactobacillus mucosae
Enterococcus

2. Short-Chain Fatty Acid Changes

Total SCFA production (72 hours):

250 mg/day: 182.2 vs. 171.3 mmol control (~+6.4%)
350 mg/day: 185.0 vs. 171.3 mmol control (~+8.0%)

Acetate production:

250 mg/day: 94.9 vs. 72.3 mmol (~+31%)
350 mg/day: 97.4 vs. 72.3 mmol (~+35%)

Note on butyrate: Absolute butyrate levels were slightly lower than control during the short in vitro fermentation window. However, several butyrate-associated bacterial taxa increased, suggesting that longer exposure or in-vivo conditions may allow microbial cross-feeding processes (acetate → butyrate) to occur.

3. Other Metabolite Changes

Valerate: +85% (250 mg/day); approximately +300% (350 mg/day)
Lactate: approximately +100% at 350 mg/day

Benefits of MicrobiomeX® Demonstrated by This Study

Based directly on the colon model findings, citrus flavonoid extract was shown to:
✓ Selectively increase microbial taxa associated with polyphenol metabolism including Roseburia and Eubacterium ramulus
✓ Support total SCFA production increases of approximately 6–8%
✓ Support approximately 31–35% increases in acetate production
✓ Demonstrate mechanistic evidence for microbial fermentation pathway modulation
✓ Increase butyrate-producing bacterial populations, consistent with longer-term butyrate effects observed in human studies

Why This Study Matters

In a validated human colon simulation model, citrus flavonoid extract selectively influenced the composition and metabolic activity of the gut microbiota. The extract increased several bacterial taxa associated with polyphenol metabolism and short-chain fatty acid production while shifting fermentation toward greater acetate production. These findings provide mechanistic evidence that citrus flavonoids can influence microbial fermentation pathways in the colon and help explain the microbial metabolite changes observed in longer human supplementation studies.*

Reference Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619629/

Big-Picture Integration with Other Studies

Study 1: Daily supplementation with 500 mg of a citrus flavonoid extract for 12 weeks was associated with shifts in gut microbial metabolism in adults with features of metabolic syndrome, including a statistically significant higher relative production of butyrate among short-chain fatty acids and a trend toward lower fecal calprotectin.
Study 2: In a validated in vitro human colon model, citrus flavonoid extract selectively increased microbial taxa associated with polyphenol metabolism (Roseburia, Eubacterium ramulus) and supported approximately 31–35% increases in acetate production, providing mechanistic support for the human supplementation findings.

MicrobiomeX® Ingredient Summary & Real-World Relevance

MicrobiomeX® is a citrus-derived flavobiotic® designed to support gut health, immune balance, and metabolic signaling by influencing how existing gut bacteria function rather than adding new bacteria or bulk fiber. It provides a standardized blend of citrus flavonoids — primarily hesperidin and naringin — that reach the colon where they are metabolized by beneficial gut microbes.

In both human clinical research and validated colon simulation models, daily supplementation with 500 mg of MicrobiomeX® was associated with shifts in microbial fermentation patterns, including a higher relative proportion of butyrate among short-chain fatty acids linked to gut barrier integrity, immune signaling, and metabolic regulation.*

MicrobiomeX® works at a low daily dose (500 mg) and does not significantly increase bacterial load or stool bulk. Instead, it supports microbial pathways involved in flavonoid metabolism and short-chain fatty acid production, which may contribute to its favorable tolerability profile. This makes it particularly well suited for individuals seeking targeted gut microbiome support without the digestive adjustment often associated with high-fiber supplements.*

Ingredient Manufacturer Website: https://microbiomex.com/

MicrobiomeX® is a clinically studied ingredient used in the following Silver Fern™ Brand product:

Targeted Prebiotic

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.