As researchers unlock the diagnostic and therapeutic promise of the human microbiome, a new roadmap highlights the urgent need for standardization, better evidence, and clinician education to transform patient care.
Perspective: The microbiome for clinicians. Image Credit: Kateryna Kon / Shutterstock
A recent perspective published in the journal Cell outlines the challenges, opportunities, and necessary actions to translate microbiome sciences into clinical practice.
Advances in sequencing and bioinformatics have enabled comprehensive mapping of the composition and functional potential of the gut microbiota, associating microbiome disruption with several human disorders. Mechanistic studies have unveiled a key role of the gut microbiome in human health and disease, sparking increased interest in its therapeutic and diagnostic potential.
Nevertheless, microbiome science has not been (fully) implemented in clinical practice due to various factors, including the heterogeneity and complexity of the human microbiome, lack of standardized protocols, logistical and methodological challenges, and limited clinician familiarity with microbiome science. Further, while biological evidence might support the application of the gut microbiome in medicine, direct clinical evidence is often insufficient, and findings frequently lack validation in large, diverse cohorts. This lack of consolidated evidence and limited clinician familiarity impede integration into routine practice.
Translating microbiome sciences into clinical practice
The human microbiome has potential for various applications as a diagnostic tool in clinical medicine. Recent research has demonstrated the microbiome’s potential as a diagnostic tool, with bioinformatics and machine learning enabling the translation of complex data into clinically relevant metrics. However, clinical implementation is limited by unresolved issues, including standardization, cost-effectiveness, and validation across diverse populations. Recent research has provided indirect or direct evidence to support the implementation of microbiome diagnostics in clinical settings.
For example, two metagenomic analyses of geographically diverse datasets identified microbial signatures that were reproducibly associated with colorectal cancer (CRC), thereby enhancing the diagnostic accuracy of fecal occult blood tests. A large cohort study of nearly 1,000 patients undergoing colonoscopy identified distinct microbiome signatures for two CRC precursors, tubular adenomas and sessile serrated adenomas, highlighting the potential of the microbiome as a tool for CRC screening.
Despite its potential, several issues preclude the exploitation of the gut microbiome as a diagnostic tool in medicine. For instance, microbiome profiling technologies have not been widely utilized, despite the progressive reduction in consumables and equipment costs. Beyond technicalities, clinical implementation faces critical challenges, including unresolved questions around standardization, clinical utility, and cost-effectiveness.
Direct-to-consumer (DTC) microbiome testing has gained popularity as a means of personalized health assessments. However, this has raised concerns regarding quality control, standardization, clinical utility, and regulatory oversight. Indeed, these tests exhibit significant analytical and methodological heterogeneity. Additionally, DTC service-provided dietary recommendations and health risk assessments often lack robust scientific substantiation, which can lead to misinterpretation. Experts have called for regulatory action to limit the dissemination of potentially misleading or clinically irrelevant information.
Actions to expedite the integration of the microbiome in clinical practice
The complexity of the gut microbiome makes designing clinical trials difficult, preventing the translatability of research into clinical practice. However, various initiatives have recently attempted to standardize several aspects of microbiome research. These include the Human Microbiome Action, the Strengthening the Organization and Reporting of Microbiome Studies (STORMS) checklist, the Microbiome Quality Control Project, and the International Human Microbiome Standards Project. Recent efforts also include international consensus statements on microbiome testing and the European Union’s legal classification of microbiota as a “substance of human origin,” aimed at harmonizing regulatory frameworks.
The promising insights in microbiome research warrant the strengthening and evolution of microbiome clinical trials to generate translatable outputs. This process will involve a series of actions, many of which are ongoing already. These (actions) include improved sample size estimation, application of statistics of clinical studies to microbiome trials, and systematic meta-analyses using guidelines such as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
Further, microbiome trials often include non-clinical primary endpoints. However, primary clinical outcomes allow a smoother translation of results into practice. Besides, relevant study populations are necessary to answer clinically pertinent needs. Notably, studies linking colorectal cancer (CRC) to microbiome signatures have often focused on patients with advanced disease, whereas screening individuals with premalignant lesions would be more impactful for public health.
Microbiome therapeutics have been studied as alternatives to conventional host-directed therapies; however, their combination with host-directed therapies remains largely unexplored but may offer synergistic benefits by targeting both host and microbiome determinants. This strategy could be intriguing as it involves targeting host and microbiome features, increasing the chances of success. Nonetheless, implementing these actions could be challenging if limited to academic settings. That is, academia lacks the pace and capacity of industry for applied research.
Academic centers are a minority compared to the healthcare network, which has much larger recruitment potential. This is particularly crucial for extensive associative studies aimed at discovering microbial biomarkers. Thus, other stakeholders beyond academia, such as industry and non-academic healthcare providers, are crucial in translating microbiome science into clinical practice. However, careful partnership is needed to balance scientific rigor with commercial interests.
Concluding remarks
Taken together, microbiome research continues to yield highly reliable and intriguing discoveries with significant implications. Microbiome diagnostics are primarily studied for evaluating disease risk, predicting therapeutic responses, or refining microbial modulation. Although nascent, these approaches are giving reliable findings that might be easily validated and reproduced in different clinical settings.
Therapeutic manipulation of microbes has undergone remarkable evolution over the past few years, from methodologically weak and anecdotal experiences to reproducible and more tailored therapeutics, some of which have already been introduced into the healthcare market.
Notwithstanding these promising insights, microbiome science remains far from incorporated into clinical medicine. Key initiatives—including research standardization, improved clinical trial design, and enhanced clinician education and collaboration are critical for the translation of microbiome science into clinical practice.