What is unknown in using microbiota as a therapeutic?

Abstract

Fecal microbiota transplantation (FMT) has been used extensively in the treatment of various gastrointestinal and extraintestinal conditions, despite that there are still a lot of missing gaps in our knowledge in the gut microbiota and its behavior. This article describes the unknowns in microbiota biology (undetected microbes, uncertain colonization, unclear mechanisms of action, uncertain indications, unsure long-term efficacy, or side effects). We discuss how these unknowns may affect the therapeutic uses of FMT, and the potentials and caveats of other related microbiota-based therapies. When used as an experimental therapy or last resort in difficult conditions, caution should be taken against inadvertent complications. Clear documentations of post-treatment events should be made mandatory, classified, and graded as in clinical trials. Further robust scientific experiments and properly designed clinical studies are needed.

Alterations of gut microbiome and effects of probiotic therapy in patients with liver cirrhosis: A systematic review and meta-analysis

“…However, some bacterial communities from the small intestine and those embedded within the intestinal mucosa have been neglected. [ 61 ] To further evaluate the efficacy of various probiotics, a comprehensive meta-analysis regarding the different etiologies of cirrhosis in the same region is needed and posttreatment events should be clearly recorded.…”

Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives

“…As is the case for many translational therapies, efficacy is not always maintained from in vitro observations through preclinical to clinical studies for a myriad of factors. Unfortunately, for many probiotics, one of these factors being that the mechanisms of action by which beneficial clinical outcomes are achieved have yet to be elucidated ( 20 ). The consequences for this mean that we are not utilising these tools to their full potential, opportunities for improving existing treatments may not be realised and we are at risk of probiotic treatments resulting in worse outcomes for particular subsets of patients ( 21 ).…”

Fecal microbiota transplantation in non-communicable diseases: Recent advances and protocols

“…Although gut sequencing technology is continuously advancing, the gut microbiota comprises a vast amount of species, with a considerable amount of the bacterial species and their role and functions still being unknown ( 190 ). This is a significant limitation as it is possible that some of these species have a major impact on the variable outcomes seen between studies.…”

“…Likewise, significant efforts and progress have been made in identifying key bacterial species that are correlated with better outcomes in FMT. It is clear, however, that the overall response to treatment involves a complex interplay between the gut microbial composition and the host ( 190 ). These unknown factors add an extra layer of variability, hence the need for detecting and uncovering the functions of other bacterial species, yet unknown, that may exert a major role in health and disease, whether alone or via bacterial competition and host interaction.…”