Why not all gut microbiome research is ready for application

Your gut microbiome acts as an organ of the human body responding to diet and environment changes, influencing body functions, and affecting how you respond in a particular way to diet or drugs. Between 2014 and 2024, the number of publications focusing on the gut microbiome in PubMed was 53,450, which represents four-fifths of the total number of publications over the last 40 years that investigated this topic. Some recent and ongoing microbiome initiatives include the Human Microbiome Action and the World Microbiome Partnership, both of which were launched in 2024, and Le French Gut project and Human Microbiome Project 2 (also known as the Integrative Human Microbiome Project). The increasing amount of research has also been accompanied by a wide coverage of microbiome research in the media, which is not always aligned with science and is unbalanced1,2,3.

Despite how much scientists have learned in recent years, some challenges need to be overcome before using recent microbiome advances in our everyday lives4,5,6. At Digestive Disease Week, one session addressed the dos and don’ts of microbiome-directed personalized nutrition in gastrointestinal diseases. “Microbiome testing is a promising area that will help monitor patients over time when other clinical data are provided and monitor gut microbiome changes after directed interventions in an individual”, said Elena Verdú, a researcher on the role of the gut microbiome in celiac disease and professor of gastroenterology at McMaster University in Ontario, Canada. “For this to happen, we need to address methodology limitations, track gut microbiome changes over time instead of at only one-time point, and integrate personalized medicine into current clinical/treatment guidelines”, Dr. Verdú said.

“It must be made clear that, as long as these products are not properly regulated, they cannot under any circumstances be used or sold as diagnostic tests or to advise patients on how to improve their dietary habits by taking specific dietary supplements. Nevertheless, there are some types of microbiota-based tests that, if fully validated, could be useful in establishing a positive diagnosis of irritable bowel syndrome, inflammatory bowel disease, or colorectal cancer. But it is also true that gastroenterology specialists should keep up to date and not close themselves off from the world of microbiota, because there is no doubt that these tests will evolve to be useful to the doctor and the patient”, said Dr. Javier Santos, gastroenterologist at the Vall d’Hebron University Hospital, Barcelona, Spain.

That being said, “we also need to consider the anxiety the results of a microbiome test with a decrease in Lactobacillus or an increase in Proteobacteria could cause in our patients, when there is not a clear intervention that will follow to treat their gastrointestinal condition, and financial burden related to the cost of these tests and online recommendations”, said Dr. Verdú.

According to Joël Doré, trained microbial ecologist and research director at INRAE, the three main challenges that microbiome research needs to overcome are: 1) Define the ‘healthy microbiome’ or the ‘microbiome associated with health’; 2) Define ways to monitor the state of host-microbes symbiosis that involve the microbiome but also host features at the gut level that affect systemic parameters (gut permeability, inflammation, and oxidative stress); 3) Provide scientific evidence of the efficacy of recommendations to improve health through the microbiome.

 

What is a “healthy” or “normal” gut microbiome?

Advice about improving gut health and the gut microbiome is everywhere, but defining a “healthy” or “normal” gut microbiome is challenging. Scientists have suggested a healthy gut microbiome resists endogenous (i.e., stomach acid) and exogenous insults (i.e., infections), maintains long-term stability, provides its host with essential nutrients, such as vitamins and fermentation byproducts, and aids in maintaining metabolic and immune functions in good shape7.

Lots of unknowns still exist about the thousands of microorganisms that inhabit the gut: approximately 20% of bacterial gene sequences have not been identified and the function of 40% of the estimated 10 million total of bacterial genes remains unknown. “We are not yet ready to quickly and convincingly identify a healthy microbiome and that is why microbiota tests are not widely accepted by gastroenterologists in the clinical setting”, said Santos. “A healthy microbiota would approximate one that can adapt and functionally recover from changing situations, even extreme ones, such as the presence of disease or exposure to antibiotics or chemotherapy”.

 

Is the gut microbiome part of the reason why everyone responds in a different way to diet?

The quality of your food staples is connected to the health of your gut microbiome and ultimately your health outcomes8,9. But rather than looking for the best food or product for achieving a healthier gut microbiome or fixing a gut issue, it is more important to focus on the whole diet. Doré explained that for individuals with symptoms that do not require to consult a healthcare professional, the best recommendation is very likely to adopt a Mediterranean or Cretan diet. For microbiome richness diversity matters and it has been shown that eating 30 different fruits, vegetables, legumes, nuts, and fresh condiments per week is the best target. It also combines with a reduction of one’s carbon footprint overall, hence benefiting one’s health and planetary health altogether.

Doré also stated that for individuals seeking improved gut health while consulting for more serious symptoms or any chronic condition that comes with intestinal symptoms, without any need to assess the microbiome at present, the best approach is to start with a good diet and add a combination of supplements that will act on gut permeability, inflammation and oxidative stress. Finally, for fortunately rare individuals with highly distorted gut microbiota and going through life-threatening conditions, science is slowly building evidence of potential benefits of fecal microbiota transfer, but this takes us a bit far from nutrition.

Given the huge variation in the gut microbiome between people -even identical twins-, it is likely that the microbiome is part of the reason why not all people respond the same way to a diet for weight loss or for tackling irritable bowel syndrome (IBS). Amandine Everard, a researcher at the Catholic University of Louvain in Brussels, explained that the overall shape of the gut microbiota including its richness and diversity as well as the abundance of specific bacteria taxa are important factors predicting response to gut microbiome targeted approaches such as probiotics, prebiotics, and postbiotics. “The diet is a major factor driving metabolic activities of the gut microbiome thereby influencing response to gut microbiome targeted approach. Other external factors such as drugs but also inherent factors including sex may also influence the response to gut microbiome approach”, said Everard.

Other studies have also found that the fecal microbiome could help predict which patients with IBS will respond to a low FODMAP diet or to probiotics, with microbial metabolites working better than gut microbiota composition alone (gut bacteria taxa)10,11,12.

The future of microbiome-directed personalized nutrition looks promising. “We could imagine that besides anthropometric, metabolic, and diagnostic parameters, biomarkers linked to gut microbiota could be used in an algorithm predicting the most appropriate intervention targeting one specific application for a specific individual. Such approaches have been developed to improve glycemic control and blood lipid profiles based on a machine learning algorithm integrating clinical and microbiome features,” said Everard. “Moreover, due to the potentially high number of factors to consider for microbiome-directed personalized nutrition, it seems relevant to imagine a healthcare system tracking individual-specific response to intervention to continuously feed this algorithm.” Findings presented during IBS Days 2024 also suggest the potential of merging patients with IBS into different groups according to their type of digestive symptoms and severity, psychological factors, diet, and lifestyle to individualize the management of IBS instead of a “one-size-fits-all” approach13.

As we celebrate World Microbiome Day 2024, it’s important to reflect on the groundbreaking research and promising developments in microbiome science. While significant strides have been made in understanding the gut microbiome’s role in personalized nutrition and health, there remain many uncertainties and challenges. These hurdles underscore the necessity for ongoing research and collaboration to fully harness the potential of microbiome science for enhancing health outcomes.

Let us recognize the pivotal role our microbial companions play in our well-being. Let’s support scientific endeavors and public awareness initiatives that advance our understanding and application of microbiome health. Together, we can foster a deeper appreciation of the complex world within us and work towards a healthier future for our health and the planet.

 

Further reading:

  1. Hanage WP. Microbiology: Microbiome science needs a healthy dose of skepticism. Nature. 2014; 512(7514):247-8. doi: 10.1038/512247a.
  2. Marcon AR, Turvey S, Caulfield T. ‘Gut health’ and the microbiome in the popular press: a content analysis. BMJ Open. 2021; 11(7):e052446. doi: 10.1136/bmjopen-2021-052446.
  3. Prados-Bo A, Rabassa M, Bosch M, et al. Online information in Spanish on probiotics, yoghurt, kefir, kombucha, fibre and prebiotics: an analysis of the quality of information and the certainty of the evidence supporting health claims. BMJ Open. 2022; 12(8):e063316. doi: 10.1136/bmjopen-2022-063316.
  4. Britton RA, Verdu EF, Di Rienzi SC, et al. Taking microbiome science to the next level: recommendations to advance the emerging field of microbiome-based therapeutics and diagnostics. Gastroenterology. 2024. doi: 10.1053/j.gastro.2024.05.023.
  5. Hoffmann DE, von Rosenvinge EC, Roghmann MC, et al. The DTC microbiome testing industry needs more regulation. Science. 2024; 383(6688):1176-1179. doi: 10.1126/science.adk4271.
  6. The Lancet Gastroenterology Hepatology. Direct-to-consumer microbiome testing needs regulation. Lancet Gastroenterol Hepatol. 2024; 9(7):583. doi: 10.1016/S2468-1253(24)00163-8.
  7. Wilmanski T, Rappaport N, Diener C, et al. From taxonomy to metabolic output: what factors define gut microbiome health? Gut Microbes. 2021; 13(1):1-20. doi: 10.1080/19490976.2021.1907270.
  8. Armet AM, Deehan EC, O’Sullivan AF, et al. Rethinking healthy eating in light of the gut microbiome. Cell Host Microbe. 2022; 30(6):764-785. doi: 10.1016/j.chom.2022.04.016.
  9. Asnicar F, Berry SE, Valdes AM, et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021; 27(2):321-332. doi: 10.1038/s41591-020-01183-8.
  10. Rossi M, Aggio R, Staudacher HM, et al. Volatile organic compounds in feces associate with response to dietary intervention in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2018; 16(3):385-391.e1. doi: 10.1016/j.cgh.2017.09.055.
  11. Wilson B, Kanno T, Slater R, et al. Faecal and urine metabolites, but not gut microbiota, may predict response to low FODMAP diet in irritable bowel syndrome. Aliment Pharmacol Ther. 58(4):404-416. doi: 10.1111/apt.17609.
  12. Gibbons SM, Gurry T, Lampe JW, et al. Perspective: leveraging the gut microbiota to predict personalized responses to dietary, prebiotic, and probiotic interventions. Adv Nutr. 2022; 13(5):1450-1461. doi: 10.1093/advances/nmac075.
  13. Byale A, Lennon RJ, Byale S, et al. High-dimensional clustering of 4000 irritable bowel syndrome patients reveals seven distinct disease subsets. Clin Gastroenterol Hepatol. 2024; 22(1):173-184.e12. doi: 10.1016/j.cgh.2022.09.019.

 

On our website, we have covered some of the most notable books on the subject:

 

We have also featured many videos from platforms like TEDx and TED Talks, as well as from medical societies and internationally recognized experts. Just to name a few: