Investigating the challenges in clinical transformation of microbiota-targeted strategies

The gap

Evidence profile

Sourced from the conclusions and future work and recommendations and inline gaps and future-work section of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 7 journals. Those papers have been cited 214 times in total.

Supporting evidence — 8 representative gaps

• Gut microbiota in chronic kidney disease-mineral and bone disorder: shared mechanisms, disease-specific signatures, and therapeutic prospects (2026) · Frontiers in Endocrinology · doi

  However, the included literature has inherent limitations: most clinical studies are small-sample observational designs with high population heterogeneity and inconsistent microbiota detection methods; randomized controlled trials (RCTs) are scarce, and findings from animal studies cannot be fully extrapolated to humans. For future research, large-scale, long-term, multicenter RCTs are warranted to clarify causal relationships by focusing on strain-specific effects, personalized dietary interventions, and multi-omics integration.

  generalconclusions
  Keywords: rcts included literature inherent limitations clinical small sample observational designs high population heterogeneity inconsistent microbiota
• The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics (2026) · Frontiers in Microbiology · doi

  Overall, current evidence highlights the gut microbiota- tryptophan-brain axis as a promising framework for understanding the pathogenesis of NDDs. A major insight is that Trp metabolism may provide both mechanistic clues and clinically relevant targets, particularly through AhR signaling, barrier integrity, and immune regulation. These findings also underscore the translational potential of interventions targeting this axis, including dietary modulation, microbiome-based strategies, and metabolite-derived therapies such as FMT and IPA-related approaches. (1) research should be prioritized: (metabolomics, microbiology,

  generalfuture work
  Keywords: axis overall current evidence highlights microbiota tryptophan brain promising framework understanding pathogenesis ndds major insight
• Gut microbiota and postoperative delirium: mechanistic integration of the “gut-liver-anesthesia axis” in the context of liver disease and perioperative intervention strategies (2026) · Frontiers in Medicine · doi

  strategies 8.5 Evidence gaps and future directions Although microbiota-based interventions have demonstrated benefits for liver-related outcomes—most notably rifaximin for HE and probiotics/synbiotics for postoperative infectious complications—direct evidence for POD prevention remains extremely limited. Several critical gaps merit emphasis. First, most available studies are associative in nature or focus on liver-specific endpoints, and it remains unclear whether causal modulation of the gut microbiota can reduce POD risk. Second, no clinical trials have specifically evaluated these interventions for POD prevention, representing a fundamental evidence gap. Third, substantial heterogeneity exists across probiotic formulations, dosing regimens, FMT protocols, patient populations, and limiting comparability and perioperative settings, considerations—particularly generalizability. Fourth, immunocompromised regarding FMT patients—require further dedicated investigation. in perioperative or thereby safety Future research should prioritize adequately powered, mechanism-informed randomized controlled trials that integrate longitudinal microbiome profiling, metabolomic analyses, and TABLE 2 Microbiota-targeted strategies in patients with liver disease: proposed mechanisms, available evidence, and current recommendation for postoperative delirium prevention.

  generalrecommendations
  Keywords: evidence microbiota liver prevention strategies gaps future interventions postoperative remains available trials perioperative patients directions
• Akkermansia muciniphila and Alzheimer’s Disease: Mechanisms, Evidence and Translational Potential (2026) · Biomolecules · doi

  Based on current evidence, A. muciniphila may be associated with AD, but its effects appear to be context-dependent. Animal studies indicate that A. muciniphila can influence immune function, metabolism, and gut–brain interactions, with potentially beneficial effects under certain conditions. Human studies suggest that A. muciniphila is generally safe and may confer metabolic benefits, supporting further clinical investigation. However, clinical findings remain inconsistent across studies, likely due to differences in study designs, population characteristics, and the lack of strain-level analysis. Practical challenges, including difficulties in large-scale cultivation, formulation, and maintaining bacterial viability in the gut, also limit clinical application. Large-scale studies with longer follow-up periods and more standardized method- ologies are still needed. Integrating multi-omics data with well-defined clinical outcomes and appropriate patient stratification may improve understanding of this field. It is also important to study A. muciniphila at the strain level to determine whether live bacteria, pas- teurized products, or postbiotics are more suitable in terms of safety and efficacy. Overall, further studies are required to clarify how A. muciniphila functions at different stages of AD and across diverse host conditions. At present, it is premature to consider it a reliable treatment option for AD. Author Contributions: J.L. and Q.L. conducted data collection and analysis, and drafted the initial manuscript. B.Z. contributed to manuscript editing and revision. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by the Natural Science Foundation of Chongqing Municipality (CSTB2025NSCQ-GPX0455, to B.-L.Z.) and Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau, 2026MSXM099, to B.-L.Z.). Institutional Review Board Statement: Not applicable. https://doi.org/10.3390/biom16050726 Biomolecules 2026, 16, 726 15 of 22 Informed Consent Statement: Not applicable. Data Availability Statement: No new data were generated or analyzed in this study. All data discussed in this review are available from the cited literature and publicly accessible databases as referenced in the text. Acknowledgments: During the preparation of this manuscript, the authors used AI-based language editing tools (e.g., ChatGPT (GPT-5.4)) for the purpose of improving grammar, spelling, and overall language clarity. The authors have reviewed and edited the output and take full responsibility for the content of this publication. Conflicts of Interest: The authors declare no conflicts of interest.

  generalfuture work
  Keywords: muciniphila clinical manuscript authors chongqing statement based effects conditions further across strain level large scale
• Current understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies (2024) · Experimental & Molecular Medicine · cited 202× · doi

  In conclusion, while the modulation of the gut microbiota shows promise as a potential strategy to slow AD progression, further research is needed to understand the underlying mechanisms in the interaction between microbiota and AD and to establish effective interventions. Treatments such as antibiotics, prebiotics, probiotics, postbiotics, FMT, and other strategies need to be explored for their ability to restore the balance of the gut microbiota and potentially mitigate AD pathology.

  generalconclusions
  Keywords: microbiota conclusion modulation shows promise potential strategy slow progression further needed understand underlying mechanisms interaction
• Editorial: Nutrition and oral microbiology: integrative perspectives for improved oral health (2026) · Frontiers in Oral Health · doi

  to such as doctors and dentists, for a greater in the need To conclude, our research topic highlights the fact that oral health interventions that modify the microbiome show potential for improving oral health outcomes across a variety of pathologies and disease conditions. There is increasing evidence to support the empirical use of dietary modifications or improving patient outcomes. This supplement use demonstrates inter-professional coordination between nutritionists, and primary healthcare providers improve understanding of the connection between nutritional choices in order to promote better oral and general health for the population. Despite promising results, the existing evidence remains limited by significant methodological heterogeneity, including differences in study populations, dietary interventions, probiotic strains, routes of administration, duration of follow-up, and selection of clinical outcomes. Future research should focus on conducting well-designed, adequately powered randomized controlled trials with standardized protocols, clearly defined clinically relevant outcomes, and integrating modern multi-omic approaches to characterize the oral microbiome. Such an approach will allow for a more reliable assessment of the causal relationships between dietary interventions, oral microbiome modulation, and oral and general health outcomes, thereby providing a stronger the development of personalized preventive and therapeutic strategies. A shift from studies primarily focused on describing the oral microbiome interventional research will be toward rigorously designed essential for translating current knowledge into evidence-based dietary and microbiome-targeted strategies for the prevention and management of oral diseases. foundation for Finally, we would like to emphasize the need for research into the use of dietary modulations on systemic health outcomes via the modulation of the oral microbiome. Some studies are already showing the oral microbiome can modulate inflammatory cytokines, nutritional status and healthy aging, emphasizing interconnectedness of oral and systemic health (8, 9). that the

  generalfuture work
  Keywords: oral microbiome health outcomes dietary interventions evidence need improving nutritional general designed modulation strategies systemic
• Targeted release of budesonide modulates key gut microbial abnormalities in immunoglobulin A nephropathy (2026) · Frontiers in Immunology · doi

  These findings highlight the gut microenvironment as a promising ther- apeutic target in IgAN and warrant further investigation into the role of gut microbiota in treatment response. Also, mechanistic understanding is limited by the absence of functional assessments, including microbial metabolites, intestinal barrier integrity, and host immune responses. Future studies with larger cohorts and longitudinal sampling are warranted to validate these preliminary observations.

  generalinline gaps
  Keywords: ndings highlight microenvironment promising ther apeutic target igan warrant further investigation role microbiota treatment response
• Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential (2025) · Frontiers in Microbiology · cited 12× · doi

  Investigating the challenges in clinical transformation of microbiota-targeted strategies, - Analyzing the mechanism of action and experimental efficacy of each microbiota-targeted strategy, - Providing new practical ideas for PF treatment, - Exploring the potential of probiotic/prebiotic intervention, Fecal Microbiota Transplantation (FMT), diet and lifestyle adjustment, and antibiotic use in PF treatment

  generalfuture-work sectionevidence 5/5
  Keywords: investigating challenges clinical transformation microbiota-targeted strategies analyzing mechanism

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