The findings, published in Cell Host & Microbe, suggest that HMGB1 protects intestinal cells and helps to maintain a healthy microbiota.

A protective mucus layer in the colon keeps gut microbes away from gut cells and helps prevent inflammation. HMGB1 typically helps gut cells cope with stress, but its role in normal mucus-based gut defense has been unclear.

So, Anne-Marie Overstreet at Cleveland Clinic in Ohio and her colleagues set out to investigate the role of HMGB1 in protecting the gut.

Keeping commensal bacteria

The researchers found that HMGB1, which is typically present in the cells lining the colon, is also present in the mucus layer that cover the colon in healthy people. In people with ulcerative colitis, HMGB1 was reduced or missing in the mucus, especially in areas with severe inflammation. 

Experiment in mice showed that HMGB1 is made by intestinal cells and released into colonic mucus in response to signals from gut bacteria. Mice lacking HMGB1 in gut cells had little to no HMGB1 in their mucus, and mice without gut bacteria had HMGB1 stuck inside their cells rather than released.

In mice lacking HMGB1 in gut cells, the researchers also found that bacteria moved closer to the gut lining and were more likely to invade it. HMGB1 appears to clump bacteria together and block their attachment to the gut lining, preventing invasion and epithelial cell damage. HMGB1 also suppresses bacterial virulence, keeping normally harmless gut microbes in a commensal state, the researchers found.

Antibacterial strategies 

In Escherichia coli, HMGB1 binds to the bacterial adhesin FimH—a protein used to stick to host cells. Further analyses revealed that HMGB1 binds to a specific part of FimH called ToH1, preventing E. coli from attaching to various types of cells, including gut cells. Mutating ToH1 reduced bacterial adhesion, and when HMGB1 was missing from intestinal cells, the gut lining was more vulnerable. 

In colon tissue from people with ulcerative colitis, the researchers found more bacteria expressing the adhesin FimH compared with tissue from healthy people. Computer modeling confirmed that as HMGB1 decreases, FimH-expressing bacteria increase. 

This result indicates that ulcerative colitis is associated with a failure of the HMGB1 defense system, allowing harmful bacteria to stick to and invade gut tissue, the authors say. Together, they add, the findings “suggest that ToH1 functions as a microbial virulence determinant and may serve as a target for developing antibacterial strategies that precisely target virulent bacteria.”

The fifth edition of IBS Days, a congress entirely dedicated to Irritable Bowel Syndrome, will take place in Bologna, Italy, from June 15 to 17, 2026, at the historic Palazzo Re Enzo. The meeting will bring together an international faculty of distinguished key opinion leaders and will open on Monday, June 15, with a postgraduate course focused on the diagnosis and most advanced therapeutic approaches for IBS.

The scientific congress will begin on Tuesday, June 16, with one of the key highlights of the event: the first European launch of the new Rome V criteria for the diagnosis of disorders of gut-brain interaction, with a particular focus on IBS. Across the meeting, experts will discuss emerging aspects of IBS pathophysiology, diagnosis and treatment, including the role of diet, the microbiota, intestinal permeability, motility, visceral sensitivity and the gut-brain axis, now recognized as a central component in functional gastrointestinal disorders.

Postbiotics are emerging as a promising frontier in healthcare, acting as key mediators between the gut microbiota and the host. Within the broader “biotic continuum” that includes prebiotics, probiotics, and postbiotics, microbial metabolites represent the final functional output of microbiota activity. These molecules can act locally on immune, endocrine, and epithelial cells, contributing to mucosal homeostasis, and may also enter the circulation, influencing the physiology of distant organs.

In this interview, Giuseppe Penna, from Humanitas University (Italy) discusses the role of postbiotics in relation to intestinal barrier integrity, dysbiosis, and systemic health. When microbial balance is disrupted, the production of beneficial metabolites may be altered, weakening several layers of the gut barrier, including the mucus layer, the intestinal epithelial barrier, and the gut vascular barrier. This process may contribute to increased intestinal permeability, often referred to as “leaky gut,” with potential consequences for multiple organs and body systems.

The interview also presents the development of a novel postbiotic obtained from a single bacterial strain through an innovative fermentation process. Unlike traditional fermented products, this preparation does not contain live or dead microbial cells, but only metabolites released during fermentation. Preclinical studies have shown its ability to modulate immune responses, interfere with biofilm production, and improve intestinal barrier function.

Based on these findings, clinical trials have been designed in patients with irritable bowel syndrome, a condition increasingly associated with altered intestinal permeability. In parallel, the postbiotic has shown potential relevance in oncology by increasing the expression of HLA class I molecules on tumor cells, which are essential for immune recognition by CD8 T cells. In preclinical models of triple-negative breast cancer, oral administration of the postbiotic enhanced the efficacy of immune checkpoint blockade.

These results have led to the design of randomized, double-blind, placebo-controlled clinical trials in triple-negative breast cancer, with further studies extended to melanoma and head and neck cancer. The upcoming results will help clarify whether this postbiotic approach can support gut barrier function and potentially enhance anticancer therapies.

In this interview, Giovanni Marasco from University of Bologna, discusses the growing evidence that links gut microbiota dysbiosis to the pathophysiology, clinical prognosis, disease progression, and treatment response of patients with inflammatory bowel disease (IBD). In the interview, the role of microbiota modulation in IBD management is discussed, starting from preventive strategies in at-risk individuals, such as avoiding unnecessary exposure to antibiotics and proton pump inhibitors, which may worsen dysbiosis.

For patients already diagnosed with IBD, diet represents a key first-line approach. In particular, the Mediterranean diet appears to exert anti-inflammatory effects and to promote the activity of bacteria involved in the production of short-chain fatty acids. The interview also reviews the use of selected probiotics in specific clinical settings, including Escherichia coli Nissle in ulcerative colitis and multi-strain probiotic blends in pouchitis, in line with available guideline recommendations.

Finally, the discussion focuses on fecal microbiota transplantation (FMT), which has shown promising signals in mild ulcerative colitis, while its efficacy in pouchitis remains less convincing. Given the heterogeneity of existing studies in terms of delivery methods, number of infusions, and donor selection, experts from Gemelli Hospital, including Franco Scaldaferri and Loris Lopetuso, have promoted consensus initiatives to design an optimal multicenter trial for mild ulcerative colitis. The results of this future study may help clarify the role of FMT in the therapeutic landscape of IBD.

The findings, published in Nature Medicine, suggest that fecal transplants from healthy donors can boost the effectiveness of immunotherapy and protect against severe side effects by shaping a healthy, anti-inflammatory gut microbiota.

Previous research suggests that the gut microbiota influences both response to immunotherapy and toxicity. But while studies indicate that fecal transplants may reduce side effects and improve immunotherapy efficacy, their safety and benefits in kidney cancer remain unclear.

Ricardo Fernandes at Western University in London, Canada, and his colleagues tested whether giving people with kidney cancer a fecal transplant from a healthy donor alongside immune checkpoint therapy is safe and beneficial.

Transplant safety

From 2020 to 2023, the researchers gave 20 people with advanced kidney cancer one full and two half doses of oral fecal transplant capsules, followed by standard immunotherapy. 

The fecal transplant itself caused only a mild gut side effect in one participant, while most immune-related side effects came from the anti-cancer therapy. About 85% of patients experienced some immune-related side effects, and half had more serious effects such as colitis or diarrhea. 

Following fecal transplant and anti-cancer therapy, 18 patients were evaluated, and half showed tumor shrinkage, including two complete responses. Participants who responded to therapy generally had fewer severe side effects than those who did not respond. 

Boosting immunotherapy

The researchers found that specific bacterial species were linked to outcomes. For example, people with diverse, anti-inflammatory gut microbes, such as Faecalibacterium prausnitzii, were protected from severe immune-related toxicities and more likely to respond to therapy. In contrast, high levels of the inflammatory bacterium Segatella copri were linked to toxicity and poor response to immunotherapy.

Specific microbial enzymes linked to inflammation were passed from donors to patients who later developed severe side effects, whereas people receiving microbes lacking these enzymes did not present such toxicities. 

This suggests that the functional traits of donor microbes, not just the presence of certain species, play a key role in how well people tolerate therapy and respond to treatment, the authors say. However, they add, “validation in larger, multicenter trials is necessary to refine donor selection, clarify microbiome−immunity mechanisms and confirm these exploratory findings.”

The findings, published in Cell Metabolism, suggest that restoring R. gnavus or supplementing isovaleric acid could be a promising microbiota–based strategy to prevent or treat atrial fibrillation. 

Atrial fibrillation has been linked to alterations of the gut microbiota, which produces compounds that affect inflammation and metabolism. However, it’s unclear which specific microbes or metabolites influence atrial fibrillation. 

Researchers led by Ning Ding at Xi’an Jiaotong University in Xi’an, China, set out to study the gut bacteria and blood metabolites of people with atrial fibrillation.

Protective effect

Compared with healthy people, those with atrial fibrillation had reduced levels of R. gnavus, which normally helps produce beneficial compounds such as short-chain fatty acids (SCFAs). 

One SCFA called isovaleric acid was also lower in people with atrial fibrillation, and lower levels of isovaleric acid were associated with higher inflammation, larger heart size, and greater risk of recurrence of atrial fibrillation after treatment. 

Next, the team tested how gut bacteria affect atrial fibrillation using mice grown without microbes, which naturally have higher risk of heart problems. When the gut bacteria of these animals were restored, the heart problems improved. Supplementing mice with R. gnavus reduced atrial fibrillation events, heart tissue scarring, and inflammation.

Preventing atrial fibrillation

Further experiments showed that R. gnavus produces isovaleric acid from the amino acid leucine through a bacterial enzyme called vorC. Isovaleric acid binds to a receptor on heart cells called GPR109A, suppressing a signaling pathway that drives inflammatory cell death. 

Giving mice isovaleric acid reduced heart problems and inflammation, the researchers found. In humans, a signaling pathway that triggers inflammatory cell death contributes to atrial fibrillation, and isovaleric acid could suppress this pathway.

Although the study mainly focused on short-chain fatty acids, other metabolites may also be involved in protecting against atrial fibrillation, the authors say. Regardless, they add, “these results reveal that the microbial metabolismof dietary leucine and the production of [isovaleric acid] play pivotal roles in preventing [atrial fibrillation] onset and progression.”

That number is not rhetorical. Byrd and colleagues quantified it in Nature Reviews Microbiology in 2018. Your skin hosts a microbial civilisation that defends against pathogens, regulates local immune responses, and produces metabolites that influence wound healing, inflammation, and, yes, how you smell. When these communities fall out of balance, the consequences range from eczema to chronic wound infection to systemic immune disruption. And until recently, detecting that imbalance required either a laboratory swab or the innovative Sequential adhesive skin patch, followed in both cases by days of waiting. Your €300 smartwatch, meanwhile, with all its sensors and all its processing power, has nothing whatsoever to say about it.

That is about to change. A new generation of biosensor-equipped wristbands is learning to read the chemical language of the skin microbiome in real time. Not by identifying individual bacterial species, which would require genomic sequencing, but by capturing the volatile organic compounds, the pH shifts, and the ion concentrations in sweat that serve as a biochemical fingerprint of microbial activity. Different bacterial populations leave different signatures. Staphylococcus species produce short-chain fatty acids like isovaleric acid. Corynebacterium species contribute thioalcohols. When the balance between these populations shifts, the chemical profile shifts with it, often hours or days before any visible symptom appears on the skin.

The engineering behind this is serious and, I must say, genuinely clever. Electrochemical biosensors using enzyme-modified electrodes can detect specific VOC-related metabolites in sweat, and Gao et al. demonstrated fully integrated sweat-sensing arrays back in 2016 in Nature. More recent prototypes use surface-enhanced Raman spectroscopy adapted for flexible substrates, achieving molecular specificity that electrochemical sensors alone cannot match. A group in Grenoble has been integrating SERS substrates into wristband formats with promising results on detecting bacterial quorum-sensing molecules. ETH Zurich has developed stretchable gold nanomesh electrodes that maintain conductivity when bent or compressed. These are not concept drawings. They are working prototypes.

What makes the latest devices genuinely interesting, however, is not the sensors alone. It is the pairing with on-device machine learning. The wristband does not attempt to tell you which bacteria are on your skin. It captures the chemical profile and classifies it against trained models that distinguish healthy microbial states from dysbiotic ones. The output is not a species list. It is a signal: your skin ecosystem is stable, or it is beginning to drift. That distinction, delivered continuously and in real time, is something medicine has never possessed before.

In France, we say “prévenir vaut mieux que guérir”. To prevent is better than to cure. It is one of those formulations that everyone endorses and almost nobody acts upon, because our entire healthcare economy is constructed around treating damage, not preventing it. Prevention requires seeing a problem before it announces itself. This is precisely what microbial sensing on the wrist makes possible. Dysbiosis on the skin is now implicated in atopic dermatitis, acne, psoriasis, and chronic wound infections. More recent work links skin microbial composition to systemic immune function. If one can detect the drift before the flare, before the infection, before the breakdown, one is not treating disease. One is intercepting it. And that, I would argue, terrifies every business model built on the assumption that the patient will wait until it is too late.

The near-term applications are already evident. Personalised skincare, for one, ceases to be guesswork. The global skincare market is worth over 180 billion dollars and most of it is built on the assumption that one cannot actually measure what a product does to the skin. A wristband that shows you, in real time, how your microbiome responds to a new moisturiser, a dietary change, or a week of poor sleep renders that assumption obsolete. The dermatology industry should be nervous. It will not be, of course, until it is too late.

But the applications that matter most are clinical, and this is where the current state of affairs crosses, in my view, from the disappointing into the negligent. Consider a post-surgical patient whose wristband detects early VOC signatures of wound infection hours before redness or fever appear. A diabetic patient whose band flags the microbial shifts that precede foot ulcers, the leading cause of non-traumatic lower limb amputation worldwide. Elderly residents in care facilities whose bands alert staff to skin breakdown before a pressure ulcer forms. Every one of these complications is currently managed after the damage is done. We wait for the wound to infect, the ulcer to open, the skin to break, and then we spend thousands treating what a fifty-euro sensor could have prevented. The intervention window moves from reactive to pre-emptive. That is not an incremental improvement. It is an indictment of every system still operating without it.

And then there is the horizon that excites me most. Within a decade, the convergence of skin microbiome data with gut microbiome profiling, genomic information, and environmental sensors points toward something we have never had: a continuous, integrated biological dashboard. Not a gadget that counts your steps and gamifies your morning walk. A system that understands your body as an ecosystem and tells you when that ecosystem is shifting, before you feel it, before your doctor sees it, before the symptom has a name. The wearable industry has spent ten years perfecting the art of telling you what already happened to your body yesterday. The next ten years will be about telling you what is about to happen tomorrow.

I am not naïve about the obstacles. The skin microbiome varies enormously between individuals, between body sites, between seasons. Sensor stability under continuous wear is unsolved. Separating meaningful biological signal from environmental noise requires work that is far from finished. And the privacy implications of continuous biological surveillance demand governance frameworks that do not yet exist. These are real problems, not details one waves away in a paragraph.

But the trajectory is set, and the people who should be paying the closest attention are not yet in the room. Hospital administrators still purchasing wound care as a reactive expense line. Insurers modelling chronic skin conditions as inevitable cost centres. Elderly care operators treating pressure ulcers as an occupational hazard rather than a preventable failure. The intelligent wristband is not coming to replace any of them. It is coming to make their current model of care look, within a few years, indefensibly late.

Apple, if you are reading this, perhaps we should talk.

Et voilà.

In this interview Ivana Gandolfi (international Diary Federation) describes the emerging concept of the food matrix, which helps explain how foods affect human health beyond the action of individual nutrients. The food matrix refers to the complex structure of a food product, including its components, the way they interact with one another, and the final physical and biochemical organization that influences digestion, absorption and nutrient bioaccessibility.

Dairy products are presented as a clear example of the matrix effect. Regular milk consumption has been associated with a reduced risk of colorectal cancer, while yogurt consumption has been linked to a lower risk of type 2 diabetes. Cheese, when consumed according to recommended portion sizes and frequency, does not appear to be associated with increased blood pressure. Overall, the interview highlights that the health effects of foods cannot always be explained by single nutrients alone, but should be interpreted through the broader concept of the food matrix.

In this interview Francesco Asnicar, from University of Trento (Italy) explores the role of the human gastrointestinal microbiome in cardiometabolic health and diet, with a particular focus on identifying individual microbial species associated with metabolic and dietary markers. By analysing more than 35,000 gut microbiome samples from healthy individuals across the UK and the US, the researchers were able to rank microbial species according to their consistently favourable or unfavourable associations with a broad panel of health-related markers.

These microbial rankings were then validated in independent publicly available cohorts, including healthy populations, case-control studies across different diseases, and longitudinal dietary intervention studies involving either personalised nutrition or probiotic supplementation. The research is now being expanded to more than 200,000 individuals, integrating dietary data, host characteristics and gut microbiome profiles. 

A specific focus is diabetes, where the findings suggest a strong association between microbiome composition and disease status, even after accounting for potential confounders such as medication, sex, age and BMI. Overall, the interview highlights how large-scale microbiome datasets can help clarify the links between nutrition, cardiometabolic health and disease, while informing the design of future longitudinal and interventional studies.

The findings, published in Cell Metabolism, suggest a gut microbiota-mediated mechanism by which a ketogenic diet can protect the lungs during sepsis.

Gut damage during sepsis allows bacteria and their by-products to reach the lungs, creating a “gut-lung connection” that may worsen injury. A ketogenic diet may help in sepsis by altering energy metabolism and gut bacteria, but it remains unclear which effects are most important for protecting the lungs.

Researchers led by Mingyuan Wei at South China Normal University in Guangzhou, China, tested the effects of a ketogenic diet on sepsis-related lung injury in mice by feeding the animals either a very high fat, no carbs diet or a standard high-carb diet for two weeks, then inducing sepsis.

Protecting the lungs

Mice on a ketogenic diet had lower death rates and less lung damage compared with mice on a standard diet. However, the benefits disappeared in mice without gut bacteria or after antibiotics. Transferring gut bacteria from mice on a ketogenic diet to other mice reduced lung injury and mortality.

The ketogenic diet changed the gut microbiota of mice by increasing the levels of specific gut bacteria, Limosilactobacillus reuteri and Lactiplantibacillus plantarum, while decreasing others such as Lactobacillus johnsonii and Lactobacillus murinus. Similar shifts were observed in people after two weeks on a ketogenic diet.

The ketogenic diet also increased the levels of a specific metabolite in the gut, blood, and lungs of mice. This metabolite, called azelaic acid, reduced death and lung injury, the researchers found.

Dietary interventions 

The production of azelaic acid depended on gut bacteria, in particular Limosilactobacillus reuteri and Lactiplantibacillus plantarum, which use an enzyme called FMO to convert dietary fat into azelaic acid. 

Further experiments indicated that azelaic acid travels from the gut to the lungs, where it activates immune cells to reduce inflammation and protect the lungs. The researchers also found that higher levels of azelaic acid in the lungs of people with sepsis were linked to better recovery.

“These findings highlight the therapeutic potential of a combined dietary-probiotic strategy for sepsis,” the authors say, “and they suggest that dissecting the mechanisms underlying [ketogenic diet] may pave the way for targeted dietary interventions that optimize both efficacy and safety in the emerging era of personalized nutrition.”