Reconditioning the Microbiome: Mechanistic and Clinical Insights Into Daily Microbiome Nutrition (DMN™)

Abstract

Daily Microbiome Nutrition (DMN™) is a next-generation prebiotic formulation crafted to nourish and strengthen the gut microbiome. It delivers three synergistic classes of prebiotics—fiber, resistant starch, and polyphenols—globally sourced from seven carefully selected plant-based ingredients. In today’s world, most people fall short on prebiotic intake, leaving beneficial gut microbes underfed and unable to produce the short-chain fatty acids (SCFAs) essential for gut and systemic health. This microbial undernourishment contributes to the buildup of harmful byproducts, disrupts microbiome balance, and fuels low-grade chronic inflammation—a driver of disease throughout the body. DMN helps reverse this cycle by feeding the right microbes, boosting SCFA production, restoring microbial balance, and reducing inflammation from within.

This white paper summarizes findings from the 2025 ProDigest M-SHIME® microbiome research study on DMN™. A once-daily 5.6 g was shown to increase production of health-promoting SCFAs (acetate, propionate, and butyrate), reduce harmful byproducts like ammonium, shift the microbiome toward a healthier composition – with increased levels of beneficial bacteria Akkermansia muciniphila and Bifidobacterium – and reduces important inflammatory markers. Collectively, these changes are indicative of a shift to a healthier, more resilient gut environment.

The research further demonstrated that double dose  (11.2 g/day) yields a dose-response effect, amplifying benefits such as SCFA production and anti-inflammatory effects. This supports twice daily DMN™ as an advanced therapeutic option for individuals with significant gut challenges (e.g. IBS or IBD) or to accelerate recovery after antibiotic use or a gut infection.

In conclusion, once-daily DMN™ offers a practical, science-backed way to nourish and fortify the gut microbiome, reduce inflammation, and promote whole-body wellness – with a higher-dose protocol available for those needing advanced therapeutic support.

Background

A healthy gut is essential to whole-body wellness—regulating digestion, immune activity, metabolic balance, hormonal signaling, and even mood. At the core of gut function is the gut microbiome, a complex ecosystem of approximately 38 trillion microbes that interact with their host largely through the bioactive compounds they produce. Chief among these are short-chain fatty acids (SCFAs)—acetate, propionate, and butyrate—metabolites that play a central role in maintaining intestinal and systemic health.

SCFAs are produced when microbes ferment prebiotic substrates—especially dietary fiber, resistant starch, and polyphenols. Each SCFA exerts distinct but complementary effects: acetate fuels colonocytes and helps regulate glucose and lipid metabolism; propionate modulates cholesterol and inflammatory signaling; and butyrate is essential for gut barrier integrity and immune tolerance. Together, SCFAs serve as the biochemical foundation for gut resilience.

Different substrates reach different regions of the colon: fiber tends to ferment proximally, resistant starch more distally, and polyphenols help shape microbial diversity and enhance fermentation efficiency across both regions. When delivered in combination, these substrates can restore a more complete and functional fermentation profile across the whole colon.

Yet modern lifestyles often deprive the microbiome of what it needs to thrive. Low-prebiotic diets dominated by ultra-processed foods reduce microbial diversity and shift fermentation toward proteolytic metabolism, leading to the accumulation of toxic byproducts like ammonium and diminished SCFA output. This dysbiotic state contributes to gut barrier dysfunction, chronic low-grade inflammation, and a broad range of gastrointestinal and systemic disorders, including IBS and IBD.

Addressing this dysfunction requires more than just increasing fiber intake. Many common fiber supplements are nonspecific, poorly tolerated, or fail to support keystone microbes. What’s needed is a targeted, multi-modal prebiotic strategy that can retrain the microbiome—amplifying beneficial fermentation while suppressing inflammatory outputs—without causing disruption or discomfort.

Mechanistic Drivers of Modern Microbiome Dysfunction

The following interrelated features define the dysfunctional microbiome state commonly seen today—each contributing to inflammation, impaired gut barrier function, and loss of microbial resilience:

• Insufficient SCFA Production: Many individuals produce inadequate levels of acetate, propionate, and butyrate—compromising gut barrier function, immune regulation, and metabolic homeostasis. Butyrate deficiency, in particular, is implicated in inflammatory conditions such as ulcerative colitis.
• Excess Harmful Fermentation Byproducts: In the absence of fermentable fibers, gut microbes shift toward proteolytic metabolism, generating toxic compounds like ammonium. Elevated ammonium is a marker of dysbiosis and correlates with increased mucosal irritation and inflammation.
• Imbalanced Microbiome Composition: Low fiber intake leads to depletion of beneficial taxa such as Bifidobacterium and Akkermansia, while promoting the growth of opportunists like Bilophila wadsworthia. This compositional shift is linked to increased intestinal permeability and symptom flares in IBS and related conditions.
• Chronic Low-Grade Inflammation: Dysbiosis and barrier dysfunction permit translocation of microbial products into circulation, driving persistent immune activation. This low-grade inflammation contributes to a wide spectrum of symptoms and chronic diseases, from fatigue and mood disturbances to metabolic and autoimmune disorders.
• Lack of Targeted, Practical Solutions: Most individuals fail to meet the required diversity and intake of prebiotics needed to support microbiome restoration. Conventional fiber supplements are often poorly tolerated, lack prebiotic variety, and fail to provide science-proven doses. There is a clear need for an evidence-based, clinically informed intervention that is effective, well-tolerated, and sustainable—both for general wellness and therapeutic use.

The Solution: Daily Microbiome Nutrition (DMN ™) by 38TERA®

Daily Microbiome Nutrition (DMN™) is a next-generation prebiotic formulation designed to restore microbial balance, increase SCFA production, and address core features of dysbiosis. It delivers three classes of microbiota-accessible nutrients—fiber, resistant starch, and polyphenols—from seven plant-based ingredients selected for their complementary fermentation profiles across the colon. Two key components, Solnul® resistant potato starch (3.5 g) and Actazin® green kiwifruit powder (600 mg), are included at the exact doses shown in human clinical trials to improve gut microbiome composition, enhance digestive function, and reduce gastrointestinal symptoms. This evidence-based design supports both structural and functional restoration of the gut ecosystem.

Study Aim

To explore how DMN™ influences gut microbial activity and structure, a laboratory-based microbiome study was conducted by ProDigest(Belgium), a globally recognized leader in intestinal microbiome research and advanced gut modeling, using a scientifically validated, human-relevant model of the colon. 

Brief Summary of Methods

The in vitro study employed the M-SHIME® (Mucosal Simulator of the Human Intestinal Microbial Ecosystem) platform, which replicates the conditions of the human colon, including both luminal (gut content) and mucosal (gut lining) environments.

This dynamic system was inoculated with gut microbiota from five healthy adult donors to account for interindividual variability and simulate a real-world range of microbial baselines. The study spanned a 15-day treatment period, during which DMN™ was administered once or twice daily to mimic human intake levels (5.6 g/day and 11.2 g/day, respectively).

Key parameters measured included:

• Short-chain fatty acid (SCFA) production – including acetate, propionate, and butyrate – to assess fermentation activity
• Ammonium levels as an indicator of proteolytic fermentation and microbial waste
• Microbial composition shifts via shallow shotgun metagenomic sequencing
• Immune signaling markers, including pro- and anti-inflammatory cytokines, to explore how microbial changes may influence host inflammation pathways

This controlled, donor-inclusive model allowed for a detailed, mechanistic understanding of how DMN™ influences microbial activity, structure, and metabolic output within the gut ecosystem.

Results

Observed Effects of Once-Daily DMN™ Supplementation (5.6 g/day)

Key outcomes associated with consistent daily DMN™ supplementation over 15 days are summarized as follows:

Increased SCFA Production

Daily supplementation with DMN™ resulted in a rapid and significant increase in the production of short-chain fatty acids. Acetate, the most abundant and structurally simple SCFA (C₂), showed a rapid rise—increasing by 12% within the first 3 days. This early surge aligns with acetate’s role as a primary fermentation product produced by a wide range of gut bacteria.

By Day 8, propionate (C₃) levels were increased 28%, reflecting the activation of microbial pathways that rely on more complex substrate processing. Butyrate (C₄), a critical energy source for colonocytes and a key anti-inflammatory molecule, increased more gradually, reaching a 22% elevation by Day 11. This delayed response is consistent with butyrate’s position in the microbial cross-feeding hierarchy, where it is often synthesized via the conversion of acetate and lactate by specialized bacterial taxa.

Importantly, the amount of DMN™ administered daily remained constant throughout the study. The continued rise in SCFA production over time suggests that the microbiome was not merely reacting to the prebiotic inputs, but adapting to them—becoming more efficient at fermenting substrates into SCFAs. This adaptive response implies that, over time, DMN™ users may not only generate more SCFAs from the product itself, but also enhance their microbiome’s ability to extract value from other dietary fibers and resistant starches in their diet.

After 15 days of daily DMN™ use, all three major SCFAs—acetate, propionate, and butyrate—were substantially elevated, supporting improved gut barrier integrity, immune regulation, and metabolic balance—key hallmarks of gastrointestinal and whole-body health.

Collectively, these findings demonstrate a robust and coordinated revival of saccharolytic fermentation, indicative of a healthier microbiome. After 15 days of daily DMN™ use, all three major SCFAs—acetate, propionate, and butyrate—were substantially elevated, supporting improved gut barrier integrity, immune regulation, and metabolic balance—key hallmarks of gastrointestinal and whole-body health.

 

Reduction of toxic metabolites

DMN™ supplementation led to a measurable reduction in ammonium (NH₄⁺) levels, with concentrations approximately 11% lower by Day 5 compared to control conditions and peaking at a 23% reduction during the study. Ammonium is a byproduct of proteolytic fermentation—the microbial breakdown of protein—which is associated with gut irritation and inflammatory signaling when overproduced. By shifting microbial metabolism away from proteolysis and toward saccharolytic (fiber-based) fermentation, DMN™ helps reduce the generation of nitrogenous waste products. This shift contributes to a cleaner, less inflammatory gut environment as endogenous toxin load is minimized.

Microbial Enrichment of Health-Associated Taxa

Consistent DMN™ supplementation led to a marked enrichment of health-associated taxa, most notably within the genus Bifidobacterium and the species Akkermansia muciniphila. These shifts were observed in both the luminal and mucosal compartments, indicating a broad and durable impact across key ecological niches of the colon.

By Day 8, early compositional changes suggested a transition toward a more saccharolytic and metabolically favorable microbial community—laying the foundation for more pronounced effects by Day 15.

At the end of the intervention, Bifidobacterium species were consistently elevated, reflecting enhanced fermentation of prebiotic fibers and resistant starches. As foundational saccharolytic organisms, Bifidobacteria produce acetate and lactate—critical substrates for downstream butyrate synthesis—and contribute to immune modulation, competitive exclusion of pathogens, and epithelial stability.

Simultaneously, Akkermansia muciniphila increased significantly in both the luminal and mucosal compartments of the colon. This mucin-degrading bacterium plays a key role in maintaining gut barrier integrity and has been consistently associated with reduced intestinal permeability, improved metabolic regulation, and lower inflammatory tone. Its abundance is now recognized not only as a robust biomarker of gastrointestinal and metabolic health, but as a keystone indicator of microbiome resilience—central to epithelial integrity, immune modulation, and long-term host vitality. In short, A. muciniphila is increasingly regarded as a sentinel species of a well-functioning gut ecosystem.

The co-enrichment of Bifidobacterium and Akkermansia reflects a coordinated microbiome remodeling effect—enhancing beneficial fermentation, reinforcing mucosal defenses, and supporting long-term digestive and immune homeostasis.

 

Suppression of Inflammatory Taxa

DMN™ supplementation led to significant suppression of inflammation-associated taxa, including Bilophila wadsworthia, which declined markedly by Day 8. This sulfite-reducing, bile-tolerant bacterium produces hydrogen sulfide (H₂S), a metabolite that—at elevated levels—compromises epithelial integrity and mucosal barrier function.

B. wadsworthia expansion, particularly under high-fat, low-fiber conditions, has been implicated in the pathogenesis of ulcerative colitis via bile acid dysregulation and immune activation. Its pro-inflammatory profile is also linked to colorectal carcinogenesis.

In conjunction with the enrichment of Akkermansia muciniphila and Bifidobacterium spp., the reduction of B. wadsworthia suggests that DMN™ induces a coordinated microbial shift—suppressing pathogenic fermentation while promoting protective commensals—supporting a transition from dysbiosis toward microbial eubiosis.

Immunomodulatory Effects and Anti-inflammatory Signaling

DMN™’s impact on microbial composition and fermentation was accompanied by a measurable shift in immune signaling, indicative of an anti-inflammatory effect. In vitro assays showed that DMN™-treated colonic suspensions reduced TNF-α by 17% and increased IL-10 by 15%.

TNF-α is a central pro-inflammatory cytokine involved in barrier disruption and immune amplification; its overexpression is implicated in IBD, rheumatoid arthritis, and other chronic inflammatory diseases, and it remains the therapeutic target of several anti-TNF biologics (e.g., infliximab, adalimumab.) IL-10, by contrast, promotes mucosal immune tolerance and regulates pro-inflammatory signaling. Its upregulation is associated with protection against gut-mediated inflammatory and autoimmune conditions.

Together, these cytokine shifts—alongside elevated SCFA production and enrichment of commensal taxa—suggest that DMN™ modulates the immune environment toward resolution and homeostasis. While derived from preclinical data, these changes provide mechanistic support for observed improvements in digestive comfort, mood stability, and reduced symptom flares.

Clinical Validation of DMN™’s Core Ingredients  While the 15-day ProDigest M-SHIME® study offers robust mechanistic insight into DMN™’s microbiome effects, its formulation is further supported by human clinical trials on its core ingredients: Solnul® resistant potato starch and Actazin® green kiwifruit powder. These studies reinforce the in vitro findings and extend the evidence base to include clinically relevant improvements in gut function, barrier integrity, and digestive symptoms. At a dose of 3.5 g/day, Solnul® has been shown in randomized, placebo-controlled trials to significantly increase Akkermansia muciniphila and Bifidobacterium—the same taxa enriched in the DMN™-treated M-SHIME® system. Solnul® has also been shown to improve tight junction integrity and reduce systemic histamine levels, consistent with improved barrier function and immune regulation—mirroring DMN™’s effects on SCFA production, ammonium reduction, and cytokine modulation. Actazin®, at 600 mg/day, has demonstrated clinically meaningful effects on bowel regularity and digestive comfort. In human trials, Actazin® increased Akkermansia abundance, improved stool form and frequency, and reduced bloating. It also enhanced levels of Faecalibacterium, a key butyrate producer—paralleling the butyrate elevation observed in the 15-day DMN™ study. Importantly, DMN™ includes Solnul® and Actazin® at the exact doses validated in clinical trials, reinforcing the scientific integrity and translational relevance of its formulation.

Dose-Response Effects of DMN™

Direct comparison of standard (5.6 g/day) and high (11.2 g/day) DMN™ dosing over 15 days revealed a clear dose-response relationship, with the higher dose yielding amplified effects across key metabolic, microbial, and immunological endpoints.

• Enhanced SCFA Production: Twice-daily DMN™ (11.2 g/day) produced a substantial increase in microbial fermentation. By Day 15, acetate rose by 44%, propionate by 56%, and butyrate by 130% relative to control. Notably, propionate and butyrate production were not only amplified, but also accelerated—with propionate rising significantly by Day 3 and butyrate by Day 5. These shifts reflect a robust, dose-dependent enhancement in both the magnitude and kinetics of SCFA output across key metabolic pathways.
• Greater Reduction in Proteolytic Fermentation: The high dose produced an even greater reduction in ammonium (NH₄⁺) levels compared to the standard dose, peaking at 24% reduction. 
• Broader Microbial Remodeling: Twice-daily DMN™ enriched a wider range of beneficial taxa, including additional fiber-degrading and SCFA-producing genera such as Gemmiger and Agathobacter. 
• Amplified Anti-inflammatory Cytokine Response: The 11.2 g/day dose produced a more robust shift in inflammatory signaling, including a greater reduction in TNF-α and larger increase in IL-10 compared to the standard dose. Additionally, monocyte chemoattractant protein-1 (MCP-1)—a chemokine involved in immune cell recruitment and chronic inflammation—was significantly reduced at the high dose. The combined downregulation of TNF-α and MCP-1, along with the upregulation of IL-10, indicates a more pronounced shift toward an anti-inflammatory immune profile.

 

Discussion

The 15-day ProDigest M-SHIME® study demonstrated that Daily Microbiome Nutrition (DMN™), when administered at clinically relevant doses, produced measurable and clinically meaningful shifts in gut microbiome function and composition. Once-daily DMN™ (5.6 g/day) led to a progressive and significant increase in all three major short-chain fatty acids (SCFAs), a reduction in ammonium as a marker of proteolytic fermentation, and enrichment of key health-associated taxa including Akkermansia muciniphila and Bifidobacterium. These changes were accompanied by a decrease in Bilophila wadsworthia and a shift in inflammatory signaling characterized by lower TNF-α and higher IL-10.

When administered at a higher dose (11.2 g/day), DMN™ produced markedly amplified effects in SCFA output and immune signaling—including a 130% increase in butyrate, a 56% rise in propionate, and a 44% rise in acetate by Day 15. These metabolic changes were accompanied by greater reductions in pro-inflammatory cytokines TNF-α and MCP-1, along with enhanced IL-10 upregulation, highlighting a strong dose-response effect across both microbial and host immune pathways. These findings mechanistically validate DMN’s effects on microbial metabolism and immune signaling, supporting its use as both a daily microbiome-supportive strategy and an intensified protocol in higher-need clinical settings.

Taken together, the results of this study directly address the key challenges facing the modern microbiome and show that DMN™ effectively counteracted the microbial undernourishment, proteolytic fermentation, and low-grade inflammation that characterize many modern gastrointestinal and systemic health concerns—bringing the microbiome closer to a state of functional resilience and metabolic balance.

Modern Microbiome Dysfunction	DMN™ Impact
Insufficient SCFA production	Acetate, Propionate & Butyrate
Excess harmful microbiome byproducts	Ammonium
Imbalanced microbiome composition	Akkermansia, Bifidobacteria Bilophila
Chronic low grade-inflammation	TNF-α IL-10

Once-Daily DMN™: A Foundation for Ongoing Gut and Immune Support

DMN™ was designed to support both everyday wellness and clinical gut health strategies through a once-daily format that emphasizes consistency, tolerability, and cumulative benefit. Its enjoyable flavor and ease of use make it simple to incorporate into daily routines—an essential factor in forming sustainable habits and achieving long-term results.

DMN™’s formulation reflects a commitment to clinical rigor and patient safety:

• Doctor-formulated by gastroenterologist Dr. Will Bulsiewicz
• Includes Solnul® (3.5 g) and Actazin® (600 mg) at doses proven in human trials
• FODMAP Friendly Certified, ensuring tolerability in sensitive populations
• NSF Certified for Sport®, with testing of raw materials, manufacturing practices, and finished product integrity

Together, these features make DMN™ a reliable, evidence-based tool for supporting microbiome function—appropriate for daily use, therapeutic protocols, and long-term gut health maintenance.

These features make DMN™ a reliable, evidence-based tool for supporting microbiome function—appropriate for daily use, therapeutic protocols, and long-term gut health maintenance.

The 15-Day DMN™ Recharge: A Short Term Strategy for Microbiome Recalibration

The 15-Day DMN™ Recharge (11.2 g/day) is designed as an intensive, short-term protocol for individuals with underlying gut or immune dysregulation—including those recovering from antibiotics, gastrointestinal infections, or managing conditions marked by dysbiosis and chronic inflammation.

As demonstrated in the ProDigest M-SHIME® study, this higher-dose approach elicits amplified effects on microbial fermentation and immune signaling, offering rapid recalibration of a disrupted ecosystem. Its clinical utility extends beyond recovery: the Recharge may also serve as a microbiome-enhancing adjunct, used periodically to increase SCFA output and anti-inflammatory tone before returning to the standard 5.6 g/day maintenance dose.

This intermittent model—akin to a metabolic reset strategy—may be employed episodically to optimize microbiome performance and reinforce resilience when needed. The 15-Day DMN™ Recharge thus offers a flexible, clinically supported approach to accelerating microbial restoration, deepening host-microbiome communication, and extending long-term benefits of daily DMN™ use.

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