The microbiome is made of up trillions of microorganisms, each playing a crucial role – good or bad – in our health and wellbeing. Varying from one organ to another, and between every individual, the microbiome is a goldmine for researchers. In this feature, we explore the state of the microbiome research landscape and highlight some key work from the last few months.
The past
The history of microbiome research can be traced back to the 1600s, when the first bacteria were identified. In the 1670s, Dutch microbiologist Antonie van Leeuwenhoek observed what he termed ‘animalcules’ in various settings, including in dental plaque. However, it took some time for these findings to influence healthcare, with ‘germ theory’ taking off as a concept in the 19th century.
Although germ theory suggested that these microorganisms were linked to disease, questions began to circulate around whether all bacteria were bad. In 1907, Élie Metchnikoff, a Russian immunologist and subsequent Nobel laureate, proposed that lactic acid bacteria in fermented foods, such as yogurt, could promote health by extending lifespan and improving digestion. His work introduced the concept of probiotics and the idea that microbes could have beneficial effects on human health. Still,microbiology work remained primarily focused on pathogenic bacteria.
The advent and mass production of antibiotics in the 20th century transformed the microbiology field, and, ultimately, our guts. Alongside the destruction of disease-causing bacteria came the wipeout of the ‘friendly’ microbes in our bodies. In response to this came the first modern fecal microbiota transplant in 1958, which aimed to reintroduce good bacteria to the gut. However, the treatment did not become commonplace.
Technical advances in the late 20th and 21st centuries, like the development of PCR, enabled researchers to detect microbial DNA directly from samples without needing to culture them. This allowed the study of a diversity of microbes that had previously been undetectable. Plus, with increasingly versatile and sensitive genomic technologies, the field of metagenomics was born. In 2007, the Human Microbiome Project was launched by the NIH. Research conducted as part of the project showed that the human body contains trillions of microbes, outnumbering human cells, and that the microbiome plays a critical role in health and disease. Another key discovery was the vast variability of microbiomes between individuals, making the microbiome an intriguing target for personalised treatment.
Following the success of the Human Microbiome Project, research in this field took off in the 2010s. The gut microbiome in particular was linked to a range of traits and disorders – including obesity, cancer, mental health conditions and more – and the first gut microbiome reference was published in 2019.
Even now, there are large areas of microbiome research that remain largely untouched. Focus has shifted primarily from the gut toother organs, including the skin and lungs. Fecal transplants have been in the news again, particularly as a treatment for C. difficile. Plus, techniques such as microbiome editing have shown potential.
The present
The microbiome has been a key topic in the life sciences world of late. Here, we share some exciting research and reviews that sum up the current landscape.
The interplay between diet and the gut microbiome: implications for health and disease (Ross et al., 2024) – This recent review explores the impact of geographical location and a range of different diets on the function and composition of the gut microbiome.
Utilization of the microbiome in personalized medicine (Ratiner et al., 2023) – Another review, this time from late-2023, which discusses the inter-individual variability of the microbiome, and its subsequent potential in personalised medicine approaches. The authors also explore the challenges of using microbiome data in this manner.
Cross-Cohort Gut Microbiome Signatures of Irritable Bowel Syndrome Presentation and Treatment (Li et al., 2024) – In this study, the authors examined several IBS cohorts to determine the microbial signatures associated with the condition. They identified IBS-enriched clusters in both the gut and mouth. The findings point towards potential new therapies.
Lung microbiome: new insights into the pathogenesis of respiratory diseases (Li, Li and Zhou, 2024) – It’s not all about the gut! This review assesses the history, composition and function of the lung microbiome, and how the microbes in this organ (once thought to be sterile) influence health and disease.
Genome-resolved metagenomics: a game changer for microbiome medicine (Kim et al., 2024) – This article from June 2024 details the capabilities and potential of genome-resolved metagenomics to study the microbiome, particularly in the gut, and how this can be used to inform microbiome-driven medicine.
Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development (Tito et al., 2024) – The gut microbiome is implicated in a range of conditions, and cancer is no exception. This study describes the microbiome profiling of hundreds of colorectal cancer patients, and compares them to previously studied cohorts, to better understand the role of the microbiome in disease and treatment.
A gut reaction? The role of the microbiome in aggression (Uzan-Yulzari et al., 2024) – The microbiome can play a role in more than health. In fact, this 2024 paper assessed the link between gut microbiome composition and aggression in humanized mice. Gut microbiome depletion – for example, after exposure to antibiotics – was associated with increased aggression.
Microbiome: Role in Inflammatory Skin Diseases (Zhang et al., 2024) – The skin microbiome also plays a crucial role in disease. This review assesses the latest research into inflammatory skin disorders, and the link between these conditions and dysregulation of the skin microbiome.
In situ targeted base editing of bacteria in the mouse gut (Brodel et al., 2024) – Perhaps one of the biggest stories of the last year, the team behind this paper used base editing to directly modify bacteria in the guts of mice. This provides a new avenue to alter the composition of the microbiome, without depletion and replacement through something like a fetal microbiota transplant.
In the spotlight
Sex differences in a mouse model of diet-induced obesity: the role of the gut microbiome – Stapleton et al., 2024.
As global obesity rates have skyrocketed, so has the need to understand the drivers behind weight gain. Diet is linked both to obesity and the composition of the microbiome, suggesting an association between the two. In addition, the rate of weight gain and microbiome composition differ between the sexes.
Given these facts, the authors of this paper set out to characterise these sex differences, hypothesising that the microbiome plays a significant role, and that microbial depletion (following antibiotic treatment) would negate these sex differences.
The study ultimately showed that although the composition of the microbiome explained some of the sex differences in weight gain in mice, it did not account for them all. In addition, the differences remained prevalent even after microbial depletion.
From FLG
Looking for more microbiome content? Our ongoing webinar series focuses on the impact of the microbiome on human health through case studies, discussion of the latest technological advancements and conversations on how discoveries can be turned into actionable insights. You can catch the webinar series live or on-demand here.
The future
The microbiome may have been studied for hundreds of years, but it’s clear that research is currently at a peak. Gut bacteria has long been the focus of many health regimes, but it’s true impact on human health and wellbeing is only now being fully realised. Plus, the study of other organs – many of which were once thought to be sterile – is pushing the field forward even more.
Many discussions about the microbiome centre around how it can be leveraged for precision medicine approaches, for example in cancer or in the treatment of infectious disease. Not only would these personalised approaches address disease caused by, or linked to, the microbiome composition, they would also focus on the fact that some individuals will metabolize drugs differently due to their microbial makeup – the topic of a field called pharmacomicrobiomics.
Crucially, however, the microbiome could one day be the key to preventative health care. This could take a variety of forms, such as early detection of microbiome changes or a better understanding of maternal-fetal microbiomes to predict future disease. Moreover, using this newfound knowledge on the microbiome to inform dietary choices could lead to decreased incidence of obesity and its related diseases.
Overall, the microbiome clearly has a significant influence over the human body, and with trillions of microorganisms finding a home within our organs, it’s hard to say we’ll ever uncover all the answers. But with advancing tech and better understanding, we’re well on the way to using the microbiome in healthcare. Beyond simply altering our diets, the microbiome can now be shaped using gene editing tools and through advanced fecal transplants, meaning the potential to exploit the microbiome is greater than ever.
