In the Journals

Review outlines future of microbiome research

The gut microbiome has become an important area of study in gastroenterology and beyond over the course of the last few decades. Research has shed light on new targets for therapy for several diseases, but a lot about the microbiome is still unknown.

As part of a series to celebrate the 10th anniversary of Science Translational Medicine, Eran Elinav, a professor in the immunology department at the Weizmann Institute in Israel, and colleagues reviewed the last 10 years of microbiome research and outlined the work that still needs to be done.

“In its infancy, such research focused on important but inherently limited descriptive studies, providing a detailed characterization of microbiome alterations during health and disease and in response to distinct dietary regimens,” they wrote. “These studies are now being followed by more mechanistic approaches to establish causal links between microbiome assemblages and various phenotypes.”

Elinav and colleagues focused on five kinds of intervention through which researchers have explored microbiome modulation.

Diet

Although people have looked to diet to treat medical conditions for many years, shifting focus onto how diet impacts the microbiome is much more recent. Elinav and colleagues described several studies that revealed the ways diet shapes the microbiome and influences a patient’s health.

“These discoveries have led to potential approaches to treat cardiometabolic disease, and attempts have been made to find prebiotic dietary components to shape the microbiome and confer health benefits on the host,” they wrote.

The authors wrote that they believe that microbiome-based dietary interventions could become important tools in the treatment of disease, such as inflammatory bowel disease.

“Fecal microbiome profiling could become a component of medical evaluation, leading to tailor-made diets or ad hoc medications,” they wrote. “Future studies should concentrate on long-term impacts and safety of such therapies and on their potential extension to health conditions beyond obesity and its metabolic complications, such as malnutrition, dietary constituent deficiencies, inflammatory states, and neoplastic diseases.”

Probiotics

Elinav and colleagues wrote that modern microbiome research allows investigators to study how microbial intervention effects the host through colonization and interaction with the microbes that are already present in the gut. Understanding these interactions could lead to personalized probiotic therapies that are designed to target each patients’ specific gut microbial environment. However, larger randomized controlled trials are needed to explore different kinds of clinical situations and population groups.

“There are still major obstacles to implementing live microbial therapy in clinical practice,” they wrote. “These challenges include the need to develop noninvasive approaches for direct sampling of the gut mucosa and technologies to enable reliable characterization of the microbiome in different regions of the gut.”

Bacterial Metabolites

The researchers wrote that these bacteria-derived metabolites have been shown to help reduce gut inflammation, accelerate weight gain and even reduce the risk for atherothrombotic events like myocardial infarction and stroke in animal models.

“Together, these findings highlight the potential of postbiotic therapy with microbiome-derived molecules in animal models,” they wrote. “Additional studies are warranted to shed light on the intended and off-target effects of such compounds and to examine their long-term safety in humans.”

Fecal Microbiota Transplantation

Fecal microbiota transplantation has been one of the biggest successes of gut microbiome research. Its efficacy for the treatment of recurrent Clostridium difficile infection has led to studies in other areas, including IBD. However, its efficacy in treating other diseases is varied depending on the donor.

Elinav and colleagues wrote that autologous FMT — which uses samples from the patient saved from before the onset of disease — could become an alternative.

“Such an approach would necessitate large-scale fecal banking facilities,” they wrote. “However, it still carries underlying risks, as microbiomes from individuals who may appear healthy could harbor causal factors of the condition to be treated, resulting in unforeseen resurgence of the disease.”

Finding out what makes some donors better than others could lead to custom-made therapies, the authors wrote.

Gut Barrier Regulation

“One unmet need is an intervention that specifically eliminates harmful members of the microbiome from the ecosystem,” Elinav and colleagues wrote. “Although antibiotics are commonly used against pathogens, they are nonspecific, inflict collateral damage both to commensal bacteria and to the host, and are associated with the emergence of antibiotic-resistant bacterial strains.”

They wrote that direct targeting of the host intestinal barrier is so far unexplored but could help regulate host-microbiome interactions.

“Emerging regulators of gut barrier function include biophysical factors such as osmotic pressure, microbiome-generated molecules, and host-related modulators,” they wrote. “Comprehensive understanding of the repertoire and mechanisms of these barrier-modulating factors is an exciting avenue of future research.” – by Alex Young

Disclosures: Elinav reports that he is a consultant for DayTwo and BiomX. The other authors report no relevant financial disclosures.

The gut microbiome has become an important area of study in gastroenterology and beyond over the course of the last few decades. Research has shed light on new targets for therapy for several diseases, but a lot about the microbiome is still unknown.

As part of a series to celebrate the 10th anniversary of Science Translational Medicine, Eran Elinav, a professor in the immunology department at the Weizmann Institute in Israel, and colleagues reviewed the last 10 years of microbiome research and outlined the work that still needs to be done.

“In its infancy, such research focused on important but inherently limited descriptive studies, providing a detailed characterization of microbiome alterations during health and disease and in response to distinct dietary regimens,” they wrote. “These studies are now being followed by more mechanistic approaches to establish causal links between microbiome assemblages and various phenotypes.”

Elinav and colleagues focused on five kinds of intervention through which researchers have explored microbiome modulation.

Diet

Although people have looked to diet to treat medical conditions for many years, shifting focus onto how diet impacts the microbiome is much more recent. Elinav and colleagues described several studies that revealed the ways diet shapes the microbiome and influences a patient’s health.

“These discoveries have led to potential approaches to treat cardiometabolic disease, and attempts have been made to find prebiotic dietary components to shape the microbiome and confer health benefits on the host,” they wrote.

The authors wrote that they believe that microbiome-based dietary interventions could become important tools in the treatment of disease, such as inflammatory bowel disease.

“Fecal microbiome profiling could become a component of medical evaluation, leading to tailor-made diets or ad hoc medications,” they wrote. “Future studies should concentrate on long-term impacts and safety of such therapies and on their potential extension to health conditions beyond obesity and its metabolic complications, such as malnutrition, dietary constituent deficiencies, inflammatory states, and neoplastic diseases.”

Probiotics

Elinav and colleagues wrote that modern microbiome research allows investigators to study how microbial intervention effects the host through colonization and interaction with the microbes that are already present in the gut. Understanding these interactions could lead to personalized probiotic therapies that are designed to target each patients’ specific gut microbial environment. However, larger randomized controlled trials are needed to explore different kinds of clinical situations and population groups.

“There are still major obstacles to implementing live microbial therapy in clinical practice,” they wrote. “These challenges include the need to develop noninvasive approaches for direct sampling of the gut mucosa and technologies to enable reliable characterization of the microbiome in different regions of the gut.”

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Bacterial Metabolites

The researchers wrote that these bacteria-derived metabolites have been shown to help reduce gut inflammation, accelerate weight gain and even reduce the risk for atherothrombotic events like myocardial infarction and stroke in animal models.

“Together, these findings highlight the potential of postbiotic therapy with microbiome-derived molecules in animal models,” they wrote. “Additional studies are warranted to shed light on the intended and off-target effects of such compounds and to examine their long-term safety in humans.”

Fecal Microbiota Transplantation

Fecal microbiota transplantation has been one of the biggest successes of gut microbiome research. Its efficacy for the treatment of recurrent Clostridium difficile infection has led to studies in other areas, including IBD. However, its efficacy in treating other diseases is varied depending on the donor.

Elinav and colleagues wrote that autologous FMT — which uses samples from the patient saved from before the onset of disease — could become an alternative.

“Such an approach would necessitate large-scale fecal banking facilities,” they wrote. “However, it still carries underlying risks, as microbiomes from individuals who may appear healthy could harbor causal factors of the condition to be treated, resulting in unforeseen resurgence of the disease.”

Finding out what makes some donors better than others could lead to custom-made therapies, the authors wrote.

Gut Barrier Regulation

“One unmet need is an intervention that specifically eliminates harmful members of the microbiome from the ecosystem,” Elinav and colleagues wrote. “Although antibiotics are commonly used against pathogens, they are nonspecific, inflict collateral damage both to commensal bacteria and to the host, and are associated with the emergence of antibiotic-resistant bacterial strains.”

They wrote that direct targeting of the host intestinal barrier is so far unexplored but could help regulate host-microbiome interactions.

“Emerging regulators of gut barrier function include biophysical factors such as osmotic pressure, microbiome-generated molecules, and host-related modulators,” they wrote. “Comprehensive understanding of the repertoire and mechanisms of these barrier-modulating factors is an exciting avenue of future research.” – by Alex Young

Disclosures: Elinav reports that he is a consultant for DayTwo and BiomX. The other authors report no relevant financial disclosures.

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