The state of gut health in the 21st century.
How we study the microbiome
We may have neglected our microbes until a few decades ago, but the study of human gut microbiota is an interdisciplinary field that has exploded in recent years. Research on gut microbes is no longer limited to microbiologists. The microbiome has caught the attention of geneticists, evolutionary biologists, epidemiologists, gastroenterologists, nutritionists, endocrinologists, hepatologists, and even neuroscientists. Experts from these disciplines are becoming aware of the vast potential that our gut microbes hold for optimizing health and preventing or combating disease.
Historically, microbiology was limited to visualization techniques, like microscopy, and the culturing of microbes (in other words, growing them in isolation in a laboratory). Thanks to recent advances, microbiologists can now use DNA in addition to microscopy and culturing. DNA studies give a much more accurate understanding of our microbiota because we can see everything – not just what is grown in a lab.
Maternal and early childhood interventions
Professor Rob Knight and his wife, fellow microbiologist Gloria Dominguez-Bello, came up with the idea of swabbing their new-born with microbiota from Dominguez-Bello’s vagina, when an emergency C-section left them with no possibility of having a natural birth. Knight had been involved in several research studies on the development of the infant gut microbiota at the University of Colorado in Boulder and was concerned that his daughter would be deprived of the health benefits associated with a vaginal delivery.
Since pioneering this experimental technique, the couple replicated it in a large clinical trial to establish whether transferring microbes from a woman’s vagina to her new-born might improve some of the short- and long-term effects of C-sections. The intervention, while simple, is effective, and preliminary results showed that the inoculated babies had gut microbiotas that were far closer to their mothers’ microbiotas compared to babies delivered by C-section but not swabbed.
Large-scale citizen science projects
Professor Rob Knight also co-founded the world’s largest citizen science microbiome project in 2012. The American Gut Project is a crowd-sourced, open platform housed in the Knight laboratory at the University of Colorado. The team analyzes stool samples from people all around the world, to learn more about the species in our guts and their impact on our health. Human stool contains about 4,000 species of bacteria – making up an estimated 70% of its contents.
A twin project, British Gut, was founded in the UK in 2014 by Professor Tim Spector – the genetic epidemiologist and author of The Diet Myth – to make the project accessible to people across the Atlantic. The samples collected by the British Gut Project are sent to the American Gut laboratory for analysis. All resulting data are open source and will form part of the Earth Microbiome Project, a “collaborative international push to characterise microbial life on Earth.”
In the future, we are likely to continue to see large-scale projects based on massive datasets and the use of machine learning to expand on existing gut microbiota knowledge.
A focus on highly personalized dietary interventions
Professor Tim Spector also co-founded the ZOE Project in Britain in 2018. The ZOE Project has developed a home test kit to track and analyze the gut, blood fat and blood sugar responses of individuals. The idea is to provide personalized nutrition guidance to improve gut health and reduce inflammation – allowing for targeted, tailored interventions for individuals as opposed to a one-size-fits-all approach, and empowering people to take their health into their own hands.
The success of the project is multi-factorial: many people are frustrated with the medical system and the diet industry, self-monitoring technology is on the rise, and interest in personalization is growing. According to Spector, “The quality of the genetic sequencing on your microbiome just wasn’t good enough, even three years ago, at an affordable price.”
Thanks to the breakthrough in artificial intelligence and machine learning, personalized nutrition has taken off.
Postbiotics and phage therapy
It’s likely that many future gut health interventions will focus on diet. The latest ‘biotics’ in the gut health sphere are postbiotics, which are “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.” These are metabolites (the product of prebiotics metabolized in our guts by probiotics). In other words, they’re short-chain fatty acids. Food-based sources of postbiotics include fermented foods, which we discussed in “How to optimize your gut health, part 1: Nutrition”. They can also be taken in supplement form.
Phage therapy is another new intervention in the gut health space. Phagocytes are the cells that destroy pathogens by engulfing and consuming them. Phage therapy involves the use of bacteriophages, which are a type of virus that infects bacteria (‘bacteriophage’ literally means ‘bacteria eater’). These phages are known for being selective in the bacteria they target, making them particularly useful for targeting harmful bacteria and leaving beneficial bacteria intact – unlike antibiotics, which tend to eliminate the good bacteria along with the bad.
Fecal microbiota transplantation
Fecal microbiota transplantation, or FMT, involves “the administration of a solution of a fecal suspension from a healthy donor into the intestinal tract of a recipient.” It’s a simple but effective procedure that has shown great promise, particularly where harmful, antibiotic-resistant bacteria such as H. pylori or C. difficile are present in the guts of recipients.
Alanna Collen offers the following compelling argument for FMT:
“Treating recurrent C. diff infections with antibiotics has about a 30 per cent cure rate. Over a million people are infected each year, and tens of thousands die. But treating C. diff with a single faecal transplant has a greater than 80 per cent cure rate. For those who relapse after the first transplant […], a second transplant brings the cure rate up to over 95 per cent. It’s hard to think of any other life-threatening disease that can be treated in a single non-surgical procedure, without the need for drugs, at a cost of just a few hundred dollars, with such a high success rate.”
‘Bioinformatics’ is the science of collecting and analyzing complex biological data such as genetic codes. Thanks to bioinformatics platforms, scientists can analyze data and visualize the composition of the gut microbiome. Stanford University’s Center for Human Microbiome Studies focuses on connecting scientists from different disciplines and leveraging technology to harness the biomedical potential of our microbiota.
The Center’s goals are to fund scientific studies focused on the connections between the microbiome and human health and disease; provide resources to include the microbiome in existing or planned studies; bring together a collaborative, multi-disciplinary network of researchers to study the microbiome; and translate findings to inform medical practice, provide therapy, and inform dietary and lifestyle habits.
Current research conducted by the Center includes genetic engineering of bacteria to heal the gut and understanding the health impact of microbiome changes that have occurred with industrialization.
Knowledge sharing and more and improved clinical trials
Given the huge interest in the field of gut health and the wide range of disciplines that can benefit from further research into the microbiota, information and knowledge sharing will become even more important in the future. We are already seeing this happen in the context of large-sale citizen science projects.
However, some researchers have pointed out one major gap in the study of the gut microbiome: many of the studies that have been conducted to date are in the pre-clinical phase, and challenges arise when we move from animal to human models, due to differences in biology.
For better understanding of the link between gut microbes and human health, we need more clinical trials (i.e. trials conducted on humans rather than animals). Researchers have also suggested that we need a gold standard of testing, at least double-blind, with bigger cohorts of subjects.
Better diagnostics and testing, narrow-spectrum antibiotics, focus on antibiotic resistance
In Missing Microbes, Martin Blaser offers several solutions to improve gut health and reduce our over-reliance on antibiotics. He highlights the need to develop new types of antibiotics to combat antibiotic resistance, urges patients and doctors alike to use antibiotics judiciously, and stresses the need for better diagnostic tools to be made available to doctors. This, he claims, should prevent doctors from prescribing antibiotics when it isn’t clear whether an infection has a bacterial or viral origin.
In cases where antibiotics are absolutely necessary, Blaser says narrow-spectrum antibiotics should be favored over broad-spectrum antibiotics, which cause more collateral damage among beneficial communities of gut microbes. While these are more expensive to develop, Blaser notes that it’s better to pay upfront than down the line with an expensive, chronic illness. This sentiment of ‘prevention is better than cure’ is echoed by Alanna Collen in 10% Human.
The final frontier in gut health research: the brain-microbiota-gut axis
The interaction between the gut, microbiome and brain is described by some as the ‘final frontier’ in gut health research. Nutritional psychiatry is a relatively new field based on the notion that the food we eat impacts how we feel emotionally. Some individuals are interested in finding complementary treatments, such as so-called ‘food mood’ interventions (now known as ‘psychobiotics’), in addition to western medicine, in an effort to improve their mood and anxiety.
Scientists are pioneering innovative methods of studying the interplay between gut health and mental health. For instance, Dr. Emma Allen-Vercoe, has developed a crude model she calls ‘Robogut’ – an oxygen-free culture chamber designed to emulate the human gut. Therapies such as vagal nerve stimulation for the treatment of common psychiatric disorders like depression and anxiety are also gaining ground. One thing’s for sure though: interest in the human gut microbiome is here to stay.