Probiotics represent promising microbiome-based therapeutic can- didates, their clinical efficacy, safety

The gap

Evidence profile

Sourced from the future-work section and future work and conclusions of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 8 journals. Those papers have been cited 46 times in total.

Supporting evidence — 8 representative gaps

• Saccharomyces boulardii CNCM I-745 Supernatant Improves Markers of Gut Barrier Function and Inflammatory Response in Small Intestinal Organoids (2025) · Pharmaceuticals · cited 4× · doi

  preclinical in vivo studies to validate the efficacy and safety of S.b.S in disease-relevant models of intestinal inflammation or infection, - fractionation and proteomic analyses to identify the molecular components responsible for the observed effects, - understanding the molecular mechanisms and active ingredients of S.b.S to support the development of novel microbiome-based or postbiotic therapies, - assessing efficacy and safety in murine models of intestinal inflammation and infection

  generalfuture-work sectionevidence 5/5
  Keywords: preclinical vivo studies validate efficacy safety disease-relevant models
• Postbiotics in Human Health: Mechanisms, Therapeutic Applications, and Future Perspectives (2026) · Journal of Pharmacology, Genetics and Molecular Biology · doi

  Sreevarshini. S1, Saranya N1*, G. Umamageshwari1 1Department of Biotechnology, Nehru Arts and Science College, Coimbatore, Tamil Nadu, India *Corresponding Author E-mail: [email protected] Abstract: Postbiotics represent a paradigm shift in microbiome-based therapeutics, offering the functional benefits of probiotics without the challenges associated with live microorganism administration. Defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as "preparations of inanimate microorganisms and/or their components that confer a health benefit on the host," postbiotics encompass a diverse array of bioactive compounds including cell wall components, metabolites, short-chain fatty acids, bacteriocins, and extracellular vesicles. This review synthesizes current evidence on the mechanisms through which postbiotics modulate host physiology, their therapeutic applications across various disease states, and the challenges and opportunities that lie ahead for clinical translation. Emerging evidence supports their efficacy in gastrointestinal disorders, metabolic diseases, immune modulation, and beyond, while their superior stability, safety profile, and standardization potential position them as attractive candidates for next-generation biotherapeutics. Keywords: Postbiotics, Biotherapeutics, Gut Microbiota Received: Jan. 18, 2026 Revised: Feb. 28, 2026 Accepted: March. 27, 2026 Published: April 22, 2026 DOI: https://doi.org/10.64062/JPGMB.Vol2.Issue2.9 https://jpgmb.com/1/issue/archive This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY NC), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. (https://creativecommons.org/licenses/by-nc/4.0/) __________________________________

  generalfuture workevidence 5/5
  Keywords: postbiotics https probiotics challenges components host evidence biotherapeutics jpgmb issue authors sreevarshini saranya umamageshwari department
• Gut-muscle axis (2026) · Quality in Sport · doi

  References 1. Marttinen M, Ala-Jaakkola R, Laitila A, Lehtinen MJ. Gut microbiota, probiotics and physical performance individuals. Nutrients. in athletes and physically active 2020;12(10):2936. doi: https://doi.org/10.3390/nu12102936. 2. Porepp ODSC, et al. Effect of probiotic supplementation on gut microbiota and sport performance in athletes and physically active individuals: a systematic review. J Diet Suppl. 2024;21(5):660-676. doi: https://doi.org/10.1080/19390211.2023.2293842. 3. Heimer M, Teschler M, Schmitz B, Mooren FC. Health benefits of probiotics in sport and exercise - Non-existent or a matter of heterogeneity? A systematic review. Front Nutr. 2022;9:804046. doi: https://doi.org/10.3389/fnut.2022.804046. 4. Min L, Ablitip A, Wang R, Luciana T, Wei M, Ma X. Effects of exercise on gut microbiota of adults: a systematic review and meta-analysis. Nutrients. 2024;16(7):1070. doi: https://doi.org/10.3390/nu16071070. 5. Teglas T, Radak Z. Probiotic supplementation for optimizing athletic performance: current evidence and strategies. Front Nutr. for microbiome-based 2025;12:1572687. doi: https://doi.org/10.3389/fnut.2025.1572687. 6. Sales KM, Reimer RA. Unlocking a novel determinant of athletic performance: the role of the gut microbiota, short-chain fatty acids, and biotics in exercise. J Sport Health Sci. 2023;12(1):36-44. doi: https://doi.org/10.1016/j.jshs.2022.09.002. 7. Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018;50(4):747-757. doi: https://doi.org/10.1249/MSS.0000000000001495. 8. Hawley JA, Forster SC, Giles EM. Exercise, the gut microbiome and gastrointestinal diseases: therapeutic impact and molecular mechanisms. Gastroenterology. 2025;169(1):48-62. doi: https://doi.org/10.1053/j.gastro.2025.01.224. 9. Mohr AE, Jäger R, Carpenter KC, Kerksick CM, Purpura M, Townsend JR, et al. The athletic gut microbiota. J Int Soc Sports Nutr. 2020;17:24. doi: https://doi.org/10.1186/s12970-020- 00353-w. 10. Dorelli B, Gallè F, De Vito C, Duranti G, Iachini M, Zaccarin M, et al. Can physical activity influence human gut microbiota composition independently of diet? A systematic review. Nutrients. 2021;13(6):1890. doi: https://doi.org/10.3390/nu13061890. 11. Cullen JMA, Shahzad S, Dhillon J. A systematic review on the effects of exercise on gut microbial diversity, taxonomic composition, and microbial metabolites: identifying research gaps doi:

  generalfuture workevidence 5/5
  Keywords: https microbiota exercise systematic review performance nutrients sport nutr athletic composition probiotics physical individuals athletes
• Black Soldier Fly (Hermetia illucens) Microbiome and Microbe Interactions: A Scoping Review (2024) · Animals · cited 26× · doi

  (5) Little to no overlap exists between the commonly isolated or identified microbes from the gut and the microbes so far tested as probiotics or pre-fermentation microbes, which represents another major gap in the literature that should be filled with future research. (6) Whether probiotics function through colonization of the BSFL gut or solely through exogenous action on the substrate has rarely been examined, and represents a third major knowledge gap. (4) Data on non-bacterial microbes (archaea, fungi, protozoa) and their interactions with BSFL are lacking, representing a gap in the litera- ture.

  generalconclusionsevidence 5/5
  Keywords: microbes probiotics represents major bsfl little overlap exists commonly isolated identified tested fermentation literature filled
• Harnessing probiotics against candidiasis: a systematic review of experimental and mechanistic evidence (2026) · Frontiers in Cellular and Infection Microbiology · doi

  Therefore, although probiotics represent promising microbiome-based therapeutic can- didates, their clinical efficacy, safety, optimal dosing strategies, and long-term outcomes remain to be established through well-de- signed clinical studies. However, these findings are derived predominantly from het- erogeneous preclinical studies, and their direct translation to clinical practice remains uncertain.

  generalconclusionsevidence 5/5
  Keywords: clinical probiotics represent promising microbiome based therapeutic didates cacy safety optimal dosing strategies long term
• Functional Significance of Probiotic Bacterial Interactions with Milk Fat Globules in a Human Host (2025) · Microorganisms · cited 9× · doi

  This review offers a comprehensive analysis of current understanding of the composi- tion and functionality of MFGs, probiotic bacteria, interactions, and the role of the MFGM in either promoting or inhibiting bacterial adhesion to the intestinal epithelium, as well as the effects these interactions have on the host. Recent research indicates that the MFGM can affect probiotic activity in the host by enhancing the viability of probiotics during transit through the gastrointestinal tract and promoting colonization, leading to beneficial health outcomes. These properties suggest that MFGM material holds significant potential as a carrier for probiotics to the intestine, contributing to positive health effects. However, significant gaps remain in understanding the precise molecular mechanisms underlying these interactions, particularly in relation to different probiotic strains and their growth, survival, and functionality in various dairy matrices. Future research should explore how MFGM composition influences the species-specific interactions with probiotics and the impact of processing conditions on MFGM functionality. Additionally, more studies are needed to assess the long-term health effects of using MFGM as a probiotic carrier. Some suggestions for future research directions are as follows: • • • • • • Investigate the interactions of probiotic survival, growth, and functionality and how different probiotic strains interact with MFGM components. Explore ways to optimize MFGM components (e.g., phospholipids, sphingomyelin, cholesterol) to enhance probiotic efficacy. Consider individual factors such as age, gut microbiota, and diet to develop tailored probiotic interventions. Expand in vivo research on the long-term effects of MFGM–probiotic combinations on gut health and immune function. Investigate how MFGM–probiotic interactions can be used in functional foods and improve viability during storage and digestion. Explore the combined effects of MFGM and prebiotics to enhance probiotic efficacy. Microorganisms 2025, 13, 223 17 of 23 • • Further investigate the mechanisms of MFGM–probiotic interactions in the gastroin- testinal tract and broader gut microbiome and host health. Assess the potential for incorporating MFGM–probiotic formulations into commercial food products. Author Contributions: W.P.W.: formal analysis, methodology, investigation, writing—original draft. M.W.: methodology, supervision. D.W.E.: methodology, supervision, funding acquisition, writing— review and editing. C.T.: conceptualization, methodology, supervision, writing—review and editing. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by the New Zealand Tertiary Education Commission Centre of Research Excellence. Data Availability Statement: Data are contained within the article. Conflicts of Interest: Authors Withanage Prasadini Wasana and Caroline Thum were employed by the company AgResearch. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  generalfuture workevidence 5/5
  Keywords: probiotic mfgm interactions effects health functionality methodology review host probiotics potential explore investigate writing supervision
• Synergistic Effect of Retinoic Acid and Lactoferrin in the Maintenance of Gut Homeostasis (2024) · Biomolecules · cited 7× · doi

  The microbiota plays an important role in regulating both innate and adaptive immune responses. When the homeostasis of the microbiota, environmental cues, and its host is dysregulated, inflammatory processes occur, and an imbalanced state is generated. If these factors persist for a long period, they might trigger the development of metabolic diseases that are mainly related to processes such as the lack of or decrease in antigenic tolerance toward the microbiota and the consequent inflammatory and inefficient regulatory response by Th17 cells and Tregs. Interestingly, both LF and RA can promote the maturation of the intestinal immune system and, consequently, reduce inflammatory processes, whereas LF can act positively on the microbiota population. This favors the establishment and growth of microbes beneficial to the host, such as Firmicutes, Bacteroides, and bifidobacteria. Probiotics, with their positive impact on gut health, have been increasingly recognized for their beneficial effects in reducing the risk of developing metabolic diseases. A balanced and diverse gut microbiota, promoted by the regular intake of probiotics, plays a pivotal role in metabolic health. Probiotics contribute to maintaining a healthy balance in the gut flora, influencing factors such as inflammation and insulin sensitivity. By fostering a favorable microbial environment, probiotics can help regulate metabolic processes, including glucose metabolism and lipid profiles. Probiotic supplementation may contribute to improved weight management, reduction of abdominal fat, and mitigation of insulin resistance. These findings suggest that incorporating probiotics into one’s diet may serve as a proactive and natural approach to support metabolic health and potentially reduce the risk of metabolic diseases, such as type 2 diabetes and cardiovascular disorders. Nevertheless, individual responses to probiotics may vary, and it is advisable to consult with healthcare professionals for personalized recommendations. With this information, we wish to highlight the importance of the microbiota and the intestinal environment in the regulation of many (if not all) immune processes of the intes- tine, and vice versa, in terms of both health and disease. Still pending is the demonstration of the synergistic regulatory effect of LF and RA in both in vivo and in vitro models of dys- biosis associated with metabolic diseases. Thus, we want to find out whether, together with the establishment of beneficial and new microbiota, these chronic inflammatory processes can modify the balanced profile of Th1 and Th2, as happens in newborns when exposed to proteins in breast milk (mainly colostrum). This condition allows the proper colonization of the intestinal microbiota, combined with proper nutrition. In conclusion, the proper use and application of the synergistic effect between bovine lactoferrin and retinoic acid appear promising. The collaborative action of these compounds Biomolecules 2024, 14, 78 16 of 22 can potentially improve therapeutic outcomes in areas such as immune modulation, cellular integrity, and other physiological functions. Further exploration of their combined effects in various contexts, supported by the information discussed in this article, may reveal new opportunities for therapeutic interventions and health promotion. As we deepen our understanding of the beneficial interaction that may result between bovine lactoferrin and retinoic acid, this synergy emerges as a compelling avenue to optimize health benefits and address a spectrum of health-related challenges, such as preventing the development of diseases such as obesity, diabetes mellitus, and other metabolic disorders. Author Contributions: Conceptualization, M.C.P.-J. and J.J.E.-C.; methodology, M.C.P.-J.; formal analysis, J.J.E.-C., O.R.G.-E., P.S.-C. and A.V.-D.; investigation, M.C.P.-J., O.R.G.-E., M.I.M.-F., M.C.P.-J., E.A.-A. and M.S.-M.; resources, J.J.E.-C. and R.V.-G.; writing—original draft preparation, M.C.P.-J., J.J.E.-C., A.V.-D. and A.M.-A.; writing—review and editing, M.C.P.-J., J.J.E.-C., I.M.R.-C., B.R.-P. and M.S.-M.; visualization, M.C.P.-J.; supervision, J.J.E.-C.; project administration, J.J.E.-C.; funding acquisition, J.J.E.-C. All authors have read and agreed to the published version of the manuscript. Funding: We thank the financial support from PAPIIT 200423, Cátedra CI-2206 and CONACyT CF19-140617. Acknowledgments: Ma. Concepción Peña-Juárez acknowledges the financial support through a postdoctoral fellowship Estancias Posdoctorales Por México Para La Formación y Consolidación De Las y Los Investigadores Por México. Conflicts of Interest: The authors declare that they have no conflicts of interest.

  generalfuture workevidence 5/5
  Keywords: microbiota metabolic health processes probiotics diseases immune inflammatory beneficial intestinal support proper plays role responses
• Gastrointestinal disorders associated with gut microbiota dysbiosis in children aged 0–3 years (2026) · Annales Academiae Medicae Silesiensis · doi

  Further research on the gut microbiota in early child- hood is essential to better understand its role in the de- velopment of chronic conditions such as allergies, autoimmune diseases, obesity, and metabolic disorders. Although the current evidence shows a strong link between dysbiosis and various health problems in children, the underlying mechanisms remain in- completely understood. Future studies should analyze in detail how the gut microbiota influences immune system development, gastrointestinal maturation, and its interactions with environmental and genetic factors. In addition, developing more precise and ac- cessible diagnostic tools, including microbiota pro- filing tests, will enable earlier detection and more effective treatment approaches. A deeper understanding of how the gut microbiome shapes long-term health has the potential to transform preventive and therapeutic strategies for chronic diseases – particularly in children – and may serve as a cornerstone for future public health interventions. Authors’ contribution Study design – A. Kwiatkowski, M. Kleinert Data collection – A. Kwiatkowski, T. Lepich Manuscript preparation – A. Kwiatkowski, J. Kwiatkowska Literature research – A. Kwiatkowski, M. Górski, R. Polaniak Final approval of the version to be published – A. Kwiatkowski, M. Kleinert, T. Lepich, M. Górski, J. Kwiatkowska, R. Polaniak REFERENCES and Rev.

  generalfuture workevidence 4/5
  Keywords: kwiatkowski microbiota health chronic diseases children future kleinert lepich kwiatkowska rski polaniak further early child

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