Gut Dysbiosis Uncovered: How Gut Diversity & Gut Barrier Function Play a Crucial Role in Maintaining Your Health 

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Table of contents

Causes & solutions

Facts

  • Up to 70% of your immune system lives in your gut, making microbial resilience your frontline defense
  • A diverse and balanced gut microbiome makes it harder for even potent pathogens to take hold
  • A single course of antibiotics can wipe out up to 30% of your gut bacteria, with some species never recovering, leading to long-term vulnerabilities
  • Low microbiota diversity is linked to a higher risk of gut issues
  • Your gut barrier is your internal firewall. When weakened ("leaky gut"), unhealthy metabolites (i.e toxins) slip through, triggering inflammation and symptoms

Introduction

The human gut microbiota plays a pivotal role in maintaining overall health. When the composition and function of this microbial ecosystem become imbalanced, we talk about gut dysbiosis. This imbalance contributes to a dysregulated gut-immune axis, referring to impaired communication and feedback loop between the gut microbiota, intestinal barrier, and the immune system1.

Although the exact prevalence of gut dysbiosis in the general, asymptomatic population is scarce, studies have shown an association between gut microbiota imbalances and various pathological conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and allergic disorders2.

Among the key modulators of gut microbiota composition, nutrition stands out as a major, modifiable factor. Dietary choices can profoundly shape the microbial community, influencing resilience against disease and overall gut health.

The importance of microbiota diversity: A key indicator of gut health

A diverse gut microbiota is a hallmark of gut health. The human gut harbors trillions of microorganisms, predominantly bacteria, but also fungi, protists, archaea, and viruses. This microbial ecosystem plays a crucial role in human physiology and health, collectively aiding digestion, synthesizing essential nutrients, and regulating immune responses3.

External stress factors, such as extreme dietary changes, infections, or antibiotic use, can disrupt this microbial ecosystem. Several human intervention studies have shown that dietary fiber intake increases gut microbiota diversity4. Conversely, other studies have found that antibiotic administration decreases microbiota diversity, often leading to incomplete restoration of microbial composition5.

Decrease of microbiota diversity can cause alteration in the abundance of bacterial-produced metabolites such as short-chain fatty acids (SCFAs). SCFAs are one of the most important metabolite categories involved in the regulation of several biological functions, playing a key role in supporting a resilient and diverse gut microbiota. A resilient microbiota, supported by adequate SCFA levels, can restore its original equilibrium, whereas a non-resilient microbiota, deprived of these essential metabolites, may shift to an altered state, driving gut dysbiosis and higher abundance of pathogenic bacteria, and hence more susceptible to diseases6. To promote SCFA production, the diet should be rich in dietary fibers found in plant-based foods such as fruits, vegetables, legumes, and whole grains.

The gut barrier: A critical defense system

The intestinal mucosal barrier, also referred to as the gut barrier, is widely recognized as a critical player in gut-immune axis maintenance as it ensures the complex crosstalk between the gut microbiota (both commensals and pathogens) and the host immune system. The gut barrier is a multilayered defense system that regulates the selective permeability of the gut.

The gut barrier acts like a smart gatekeeper for your intestines. It helps keep your gut balanced by letting in the good stuff, like nutrients and blocking out harmful substances such as bacteria and toxins. This careful control helps maintain a healthy gut environment, which is called gut homeostasis7.

One important factor that affects the gut barrier is the gut microbiota. An in vivo study has shown that the gut microbiota can directly influence how "leaky" the gut barrier becomes. The study showed that high abundance of unhealthy bacteria, such as Proteobacteria (incl. E. coli), was associated with a disrupted barrier. This suggest that a shifts in microbiota composition can compromise the gut barrier function8. Contrary, certain good bacteria, like Bifidobacterium, have been shown to reduce inflammation and help strengthen the gut barrier by supporting the tight junctions9.

Key consequences linked to reduced microbiota diversity and a disrupted gut barrier

  • Reduced microbiota diversity can decrease the production of essential metabolites like SCFAs, leading to gut dysbiosis.
  • Dysbiosis can increase pathogenic bacteria and reduce gut resilience.
  • Disrupted gut barrier function allows harmful substances to pass into the bloodstream. Once in the blood, these substances can trigger the body's immune system and cause widespread inflammation, which over time may lead to long-term diseases."
  • Reduced microbiota diversity and disrupted gut barrier integrity are associated with various pathological conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and food allergies.

Restoring and protecting gut health

Functional ingredients with health benefits

The increasing demand for functional foods, beverages and dietary supplements reflects growing consumer interest in products that offer health benefits beyond basic nutrition. As healthcare shifts from reactive to proactive approaches, preventative strategies are gaining traction. Foods, beverages, and supplements containing ingredients like probiotics, prebiotics, and postbiotics are becoming more common, supported by an increasing number of human intervention studies that demonstrate the safety and efficacy of these ingredients10,11.

Several novel food ingredients today are addressing gut dysbiosis and gut barrier function:

  • Probiotics: Strains within the species such as Lactobacillus and Bifidobacterium have historically shown to help restore microbial balance by competing with pathogenic microorganisms for available nutrients and attachment sites in the intestine, producing antimicrobial metabolites (like SCFA), and enhancing gut homeostasis12.
  • Prebiotics: The most widely tested and used prebiotics are galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS), with human milk oligosaccharides (HMOs) recently being used for both infants and adults. These prebiotics promote the growth of beneficial gut bacteria like Bifidobacterium and Lactobacillus, support gut barrier function, and reduce inflammation13,14.
  • Synbiotics: Combine probiotics and prebiotics to enhance gut resilience by promoting the growth of beneficial bacteria and supporting their activity. This combination improves gut barrier function and reduces inflammation15.
  • Post-biotics: Bioactive compounds produced by probiotics during fermentation or metabolism. These compounds provide several health benefits, even after the probiotics have died or been removed. Postbiotics are gaining more and more recognition for their potential role in supporting gut health and overall well-being16.
  • Immunoglobulin Y (IgY): A natural antibody from egg yolk, supports immune health by neutralizing pathogenic agents such as rotavirus17.
  • Colostrum: Primarily derived from bovine sources, is rich in immunoglobulin G (IgG) supports mucosal immunity, gut healing, and recovery from stress or exercise18.

Binding proteins: The next frontier in gut health

Innovative gut-stabilizing ingredients that leverage natural mechanisms for enhanced gastrointestinal support.

Binding Proteins: A novel class of functional ingredients derived from camelid immunoglobulin G (IgG) binding domains, inspired by the protective properties of immunoglobulins naturally found in colostrum and raw milk that has a long history of safe ingestion. They are very target specific, designed to selectively bind and neutralize microbial-derived risk factors19,20.

Maintains microbiota diversity

Binding proteins have been shown to positively impact microbiota diversity (both alfa and beta) and promote a stable gut microbiota in vivo21. Studies have also demonstrated that binding proteins can block pathogenic bacteria while supporting the proliferation of beneficial bacteria, such as lactobacilli, thereby contributing to a healthy gut microbiota (Ferreres et al. Manuscript in preparation). By fostering a balanced microbial environment, binding proteins help reduce the need for antibiotics, which, although effective, can negatively impact the gut microbiota diversity. Reducing antibiotic use further supports the maintenance of a diverse and resilient gut microbiota.

Figure: alfa-diversity
Figure: Beta-diversity/ Binding proteins impact stability and maturation earlier
Figure: Lower abundance of E. coli in Binding protein group – Jenkins et al.

Supports a healthy gut barrier

Binding proteins help maintain the normal function of the gut lining. An in vivo study has demonstrated that they significantly contribute to the gut defense system by enhancing gut integrity under challenges, such a ETEC infection. This without inducing inflammation shown by preserving small intestinal tight junction levels (Xu et al. 2024, In review, JASB).

Figure: Tight junction from pigs -- Xu et al.

Additionally, cell models have shown that Binding Proteins can suppress the colonization of unhealthy bacteria, such as ETEC, thereby help keep the integrity of the intestinal lining and provide protection against pathogenic threats (Petersson et al. 2025 In review, Gut microbes).

Maintains hydration & electrolyte levels

Binding proteins contribute to the gut defense system. Both in vitro and in vivo data demonstrate that they prevent the entry of harmful metabolites, such as bacterial toxins, into intestinal cells. By neutralizing the destructive activity of the toxins, binding proteins help maintain intestinal integrity and contribute to the regulation of gut fluid and electrolyte balance. This regulation supports the reduction of diarrhea and excessive fluid secretion, highlighting their capacity to promote fluid and electrolyte homeostasis (Petersson et al. 2024, Nature Communications and Xu et al. 2024, In review, JASB).

Figure: Reduction of diarrhea and excessive fluid secretion - Xu et al. 2024, In review, JASB

Facts about antibiotics

WHO European Region (2023): A cross-sectional survey across 14 member states found that 50% of participants had taken antibiotics in the past year, often for ailments like colds (24%) and sore throats (21%). Alarmingly, 84% lacked proper knowledge about appropriate antibiotic use, and only 37% recalled receiving information on avoiding unnecessary antibiotics.

Factors that reduce microbiota diversity and impact gut barrier integrity

  • Antibiotic use: Broad-spectrum antibiotics can significantly diminish the diversity of gut microbiota by indiscriminately eliminating both harmful pathogens and beneficial bacterial species.
  • Pathogenic disruption: Pathogenic bacteria reduce microbiota diversity by outcompeting beneficial bacteria for nutrients, producing toxins that triggering inflammation and intestinal cell disruption.
  • Restricted diets: Low-fiber, very low-calorie, and high-protein/low-carbohydrate diets as well as the consumption of ultra-processed foods can reduce microbiota diversity by depriving beneficial bacteria of essential nutrients while promoting imbalances that disrupt gut homeostasis.
  • Environmental factors: Exposure to environmental pollutants and toxins can negatively impact the composition and diversity of gut microbiota. For instance, certain chemicals may alter microbial communities, leading to reduced diversity.

References

  1. Stolfi, C., Maresca, C., Monteleone, G. & Laudisi, F. Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases. Biomedicines vol. 10 Preprint at https://doi.org/10.3390/biomedicines10020289 (2022).
  2. Duan, H. et al. Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies. Critical Reviews in Food Science and Nutrition vol. 62 Preprint at https://doi.org/10.1080/10408398.2020.1843396 (2022).
  3. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, (2010).
  4. Cronin, P., Joyce, S. A., O'toole, P. W. & O'connor, E. M. Dietary fibre modulates the gut microbiota. Nutrients vol. 13 Preprint at https://doi.org/10.3390/nu13051655 (2021).
  5. Patangia, D. V., Anthony Ryan, C., Dempsey, E., Paul Ross, R. & Stanton, C. Impact of antibiotics on the human microbiome and consequences for host health. MicrobiologyOpen vol. 11 Preprint at https://doi.org/10.1002/mbo3.1260 (2022).
  6. Dogra, S. K., Doré, J. & Damak, S. Gut Microbiota Resilience: Definition, Link to Health and Strategies for Intervention. Frontiers in Microbiology vol. 11 Preprint at https://doi.org/10.3389/fmicb.2020.572921 (2020).
  7. Wells, J. M. et al. Homeostasis of the gut barrier and potential biomarkers. American Journal of Physiology - Gastrointestinal and Liver Physiology vol. 312 Preprint at https://doi.org/10.1152/ajpgi.00048.2015 (2017).
  8. Jakobsson, H. E. et al. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep 16, (2015).
  9. Ruiz, L., Delgado, S., Ruas-Madiedo, P., Sánchez, B. & Margolles, A. Bifidobacteria and their molecular communication with the immune system. Frontiers in Microbiology vol. 8 Preprint at https://doi.org/10.3389/fmicb.2017.02345 (2017).
  10. Davani-Davari, D. et al. Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods vol. 8 Preprint at https://doi.org/10.3390/foods8030092 (2019).
  11. Dronkers, T. M. G., Ouwehand, A. C. & Rijkers, G. T. Global analysis of clinical trials with probiotics. Heliyon vol. 6 Preprint at https://doi.org/10.1016/j.heliyon.2020.e04467 (2020).
  12. Chandrasekaran, P., Weiskirchen, S. & Weiskirchen, R. Effects of Probiotics on Gut Microbiota: An Overview. International Journal of Molecular Sciences vol. 25 Preprint at https://doi.org/10.3390/ijms25116022 (2024).
  13. Schönknecht, Y. B., Moreno Tovar, M. V., Jensen, S. R. & Parschat, K. Clinical Studies on the Supplementation of Manufactured Human Milk Oligosaccharides: A Systematic Review. Nutrients vol. 15 Preprint at https://doi.org/10.3390/nu15163622 (2023).
  14. Mei, Z., Yuan, J. & Li, D. Biological activity of galacto-oligosaccharides: A review. Frontiers in Microbiology vol. 13 Preprint at https://doi.org/10.3389/fmicb.2022.993052 (2022).
  15. Markowiak, P. & Ślizewska, K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients vol. 9 Preprint at https://doi.org/10.3390/nu9091021 (2017).
  16. Liu, Y., Wang, J. & Wu, C. Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics. Frontiers in Nutrition vol. 8 Preprint at https://doi.org/10.3389/fnut.2021.634897 (2022).
  17. Wang, X., Song, L., Tan, W. & Zhao, W. Clinical efficacy of oral immunoglobulin Y in infant rotavirus enteritis: Systematic review and meta-analysis. Medicine 98, (2019).
  18. Dziewiecka, H. et al. A Systematic Review of the Influence of Bovine Colostrum Supplementation on Leaky Gut Syndrome in Athletes: Diagnostic Biomarkers and Future Directions. Nutrients vol. 14 Preprint at https://doi.org/10.3390/nu14122512 (2022).
  19. Fiil, B. K. et al. Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets. iScience 25, (2022).
  20. Petersson, M., Thrane, S. W., Gram, L., Muyldermans, S. & Laustsen, A. H. Orally delivered single-domain antibodies against gastrointestinal pathogens. Trends in Biotechnology vol. 41 Preprint at https://doi.org/10.1016/j.tibtech.2023.01.015 (2023).
  21. Jenkins, T. P. et al. Protecting the piglet gut microbiota against ETEC-mediated post-weaning diarrhoea using specific binding proteins. NPJ Biofilms Microbiomes 10, (2024).
The Role of Binding Proteins in Gut Health

The Role of Binding Proteins in Gut Health

Gut health is essential for overall well-being, yet lifestyle habits, environmental factors such as diet, and medicines contribute to an increasing prevalence of gut dysbiosis and a compromised gut lining. These disruptions can have significant health implications, ranging from acute digestive discomfort to long-lasting challenges and broader systemic effects1. In fact, the U.S. microbiome has lost over 30% of its bacterial diversity — mainly due to antibiotics and poor diet2, 3.

How to Fix a Gut Microbiome Ravaged by Antibiotics

A diet rich in diverse carbohydrates outperforms faecal transplants in mice at restoring microbial diversity, which has been linked to a range of health conditions

Recent Research Found a Surprising Link Between Coffee and Gut Health

Coffee is more than just a daily habit—it may play an active role in shaping a healthier gut. A recent large-scale, multi-cohort study has uncovered a strong and reproducible association between coffee consumption and the enrichment of Lawsonibacter asaccharolyticus, a gut microbe linked to anti-inflammatory effects. Using integrated multi-omic data and in vitro experiments, the researchers identified quinic acid—found in coffee—as a potential driver of this microbial response. This study offers compelling evidence of a direct biochemical connection between specific dietary components and beneficial shifts in the gut microbiome.