Alteration of the Intestinal Microbiome
This review describes two potential interventions – FMT and probiotics – aimed at restoring the normal gut flora. As the intestinal microbiome and its alteration is intricately linked with both gastrointestinal and nongastrointestinal disease processes, characterizing this association is critical. In many ways, FMT is the 'ultimate probiotic,' although as described above is significantly more invasive than oral intake of a daily probiotics capsule. For these reasons, directly comparing these two interventions is challenging. Although the aim of FMT and probiotics is similar, FMT has demonstrated significantly more success in the management of recurrent CDI and possibly IBD. The data for probiotics are less strong, likely due to a lower viable bacterial dose reaching the intestine in contrast to a direct deposit of multistrain stool to an FMT recipient. As research progresses and gut flora is further characterized in patients, a long-term goal would be to develop a true probiotic that matches the bacterial strains seen in FMT at the appropriate dose and reaching the targeted destination. Ideally, this noninvasive, more publically acceptable, effective treatment could then be applied to other gastrointestinal and nongastrointestinal diseases and evaluated with randomized controlled trials.
There are multiple areas of potential research to further elaborate on the relationship between microbiome alteration and disease. In the setting of CDI, there is information lacking on the significance of gender, age, ethnicity and geographic location. For example, it is unknown if there are significant differences in the microbiome of an elderly, African-American woman from the USA compared with a middle-aged, Caucasian man in Europe compared with a young Chinese woman living in Asia. Furthermore, with increasing prevalence of community-acquired CDI, the microbiome of affected individuals living in the community is likely different from hospital-acquired cases. Specific to FMT, there is a need for additional randomized controlled trials, including as first-line therapy for CDI, as management for other gastrointestinal diseases, and as adjuvant therapy to other currently accepted treatments. Additionally, there are ongoing discussions about the potential benefit of frozen stool, synthetic stool and the utility of stool banks to ease the identification of stool donors. As we learn more about the relationship between gut flora and the immune system, it would also be beneficial to better understand immunoglobulin levels and other serum biomarkers pre- and post-FMT. As safety is paramount, there is a need for studies to examine the long-term risks and benefits of FMT and probiotics, including in immunocompromised hosts. On a broader, public health level, there is an opportunity to also discuss the impact on health policy (e.g., who should pay for donor screening costs) and regulatory impacts (e.g., what is the role of the Food and Drug Administration) on the interventions described above (Box 2).
Conclusions
This review describes two potential interventions – FMT and probiotics – aimed at restoring the normal gut flora. As the intestinal microbiome and its alteration is intricately linked with both gastrointestinal and nongastrointestinal disease processes, characterizing this association is critical. In many ways, FMT is the 'ultimate probiotic,' although as described above is significantly more invasive than oral intake of a daily probiotics capsule. For these reasons, directly comparing these two interventions is challenging. Although the aim of FMT and probiotics is similar, FMT has demonstrated significantly more success in the management of recurrent CDI and possibly IBD. The data for probiotics are less strong, likely due to a lower viable bacterial dose reaching the intestine in contrast to a direct deposit of multistrain stool to an FMT recipient. As research progresses and gut flora is further characterized in patients, a long-term goal would be to develop a true probiotic that matches the bacterial strains seen in FMT at the appropriate dose and reaching the targeted destination. Ideally, this noninvasive, more publically acceptable, effective treatment could then be applied to other gastrointestinal and nongastrointestinal diseases and evaluated with randomized controlled trials.
There are multiple areas of potential research to further elaborate on the relationship between microbiome alteration and disease. In the setting of CDI, there is information lacking on the significance of gender, age, ethnicity and geographic location. For example, it is unknown if there are significant differences in the microbiome of an elderly, African-American woman from the USA compared with a middle-aged, Caucasian man in Europe compared with a young Chinese woman living in Asia. Furthermore, with increasing prevalence of community-acquired CDI, the microbiome of affected individuals living in the community is likely different from hospital-acquired cases. Specific to FMT, there is a need for additional randomized controlled trials, including as first-line therapy for CDI, as management for other gastrointestinal diseases, and as adjuvant therapy to other currently accepted treatments. Additionally, there are ongoing discussions about the potential benefit of frozen stool, synthetic stool and the utility of stool banks to ease the identification of stool donors. As we learn more about the relationship between gut flora and the immune system, it would also be beneficial to better understand immunoglobulin levels and other serum biomarkers pre- and post-FMT. As safety is paramount, there is a need for studies to examine the long-term risks and benefits of FMT and probiotics, including in immunocompromised hosts. On a broader, public health level, there is an opportunity to also discuss the impact on health policy (e.g., who should pay for donor screening costs) and regulatory impacts (e.g., what is the role of the Food and Drug Administration) on the interventions described above (Box 2).
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