This study, published in Nature Communications mapped early-life patterns of microbial conjugated bile acids (MCBAs) and their connection to islet autoimmunity.

Bile acids (BAs), derived from cholesterol and produced in the liver, play crucial roles in lipid absorption and signaling in the gut. They are modified by gut microbes into a variety of secondary BAs, with a significant portion recirculated to the liver through enterohepatic circulation. Recent findings indicate that gut microbes can also reconjugate BAs, leading to the identification of MCBAs. These compounds interact with various receptors, influencing metabolism and immune responses. Dysregulated BA levels are linked to several diseases, including type 2 diabetes and inflammatory bowel disease. 

This longitudinal study aims to explore the trajectories of MCBAs in relation to islet autoimmunity and type 1 diabetes of children (n= 74, 3-36 months) through collection of stool samples (n=303). The study focuses on children who developed multiple autoantibodies, single autoantibodies, and those who remained negative for autoantibodies, as well as the interplay between MCBAs and gut microbiota.

A total of 110 MCBAs were examined, revealing how:

• 78 present in at least one sample, with primary bile acids (CA, Chenodeoxycholic Acid, CDCA) being more prevalent than secondary (Deoxycholic Acid, DCA; Ursodeoxycholic Acid, UDCA; Hyodeoxycholic Acid, HDCA)
• Various factors influenced MCBA profiles being the age  the primary determinant affecting 48 MCBAs
• After the first year, primary BA amidates declined, while secondary BA amidates increased, stabilizing or slightly decreasing by 24 to 36 months. Different trends were noted for HDCA conjugates, with some decreasing and others increasing with age. 
• Nine MCBAs differed by sex, and three were associated with breastfeeding duration, indicating the complexity of early-life bile acid metabolism

MCBAs and islet autoimmunity

Concentrations of ten MCBAs differed significantly between children who developed islet autoantibodies (P1Ab and P2Ab groups) and the controls. Notable findings include:

• Lower DCA conjugates in the P1Ab group compared to controls, while CDCA-Tyr showed an opposing trend
• Different age cohorts demonstrated inconsistencies in MCBA profiles across time points, yet specific conjugates remained significantly altered, with only UDCA-Asn consistently lower in the P2Ab group at 12 months
• Bacterial communities correlated with altered BA profiles, especially DCA conjugates, identifying 72 bacterial strains with associations to these metabolites, such as Eubacterium eligens and Bacteroides fragilis. Indeed, numerous microbial strains were found capable of producing specific MCBAs, supporting the role of gut bacteria in BA metabolism and their potential influence on islet autoimmunity development.

MCBAs modulate host immune responses

MCBAs were investigated for their immunomodulatory effects on the innate immune system, focusing on responses to lipopolysaccharide (LPS) in human whole blood cultures showing: 

• Various bile acid conjugates displayed different impacts on LPS-induced signaling pathways downstream of the TLR4 receptor, with unconjugated UDCA and certain conjugates inhibiting signaling, while others enhanced it
• Examining the effects of MCBAs on the adaptive immune system during the differentiation of Th17 and iTreg cells it was showed how UDCA-Asn and CDCA-Ser promoted Th17 differentiation and IL-17a secretion, while inhibiting iTreg cell differentiation
• Unconjugated UDCA and CDCA-Tyr did not affect iTreg populations but reduced IL-17a secretion, inhibiting Th17 differentiation
• RAR-related orphan receptor alpha (RORα) expression in Th17 cells appeared to correlate with IL-17A levels following treatment with these MCBAs, indicating a potential role in bile acid-mediated modulation of immune responses

To summarise, this study track microbially conjugated bile acids through early childhood, revealing their key role in islet autoimmunity development. Not only. These gut bacteria-modified bile acids strongly correlate with microbiome composition and actively shape the balance between pro-inflammatory Th17 and regulatory Treg immune cells — positioning MCBAs as crucial influencers of immune development.

In this closing interview from PPPP 2026 in Lecce, Prof. Flavia Indrio reflects on the main take-home messages from the congress, which brought together 32 leading international experts in microbiota research, allergy, nutrition, gut-brain axis and lung disease. Among the strongest themes to emerge was the importance of early-life intestinal colonization, with breastfeeding, avoidance of unnecessary C-sections and prompt management of dysbiosis identified as key factors in shaping health trajectories later in life. Indrio also highlights the growing clinical relevance of gut-brain axis research, which is beginning to open new therapeutic perspectives in severe pediatric conditions such as autism spectrum disorders and cognitive development disorders. 

A central focus of her interview is a 10-year follow-up study on newborns supplemented with Lactobacillus reuteri during the first three months of life, showing that beneficial effects may persist over time. The interview also touches on new insights into allergy, the interplay between microbiome and epigenetics, and the pivotal role of nutrition as a driver of intestinal colonization. The next PPPP meeting, she announces, will take place in Mexico City in March 2028, with broader involvement from the Latin American scientific community.

In this interview Paul Wilmes, University of Luxembourg, explores the concept of infective competence within a One Health framework, describing it as the collective capacity of microbiomes to harbor and transmit virulence factors, antimicrobial resistance genes, biosynthetic gene clusters, toxins, and other disease-relevant determinants. 

By integrating metagenomic, metatranscriptomic, metaproteomic, and metabolomic data from the same samples, the work aims to reconstruct interaction networks within microbial communities and identify how their emerging properties may causally influence human disease pathways. 

Central to this approach is the PathoFact pipeline, used to systematically profile infective competence across diverse microbiome reservoirs, including humans, animals, the built environment, and natural ecosystems. The interview highlighted findings from hospital settings, community transmission of SARS-CoV-2, animal antimicrobial exposure, wastewater treatment systems, and glacier-fed streams, showing how different environments shape gene flow and resistance dynamics. Additional results linked oral-to-gut microbial transmission with inflammatory signatures in type 1 diabetes. To move from association to mechanism, the research program is expanding its HUMIX microfluidic model and coupling high-throughput experiments with advanced AI methods to identify causal molecules and host interactions. Overall, the talk positioned infective competence as a unifying concept for studying how interconnected microbiome reservoirs contribute to health and disease in the broader context of planetary change.

The findings, published in Science Immunology, suggest that these intestinal cells, rather than immune cells, are the key sensors of beneficial microbes, helping maintain gut health and prevent inflammation.

Scientists have known that macrophages depend on signals from gut microbes to develop properly, and when this process fails, chronic diseases such as inflammatory bowel disease can occur. Although sensors called Toll-like receptors on the surface of immune cells help detect microbes, what guides macrophage recruitment is unclear.

So, researchers led by Ming-Ting Tsai at Baylor College of Medicine in Houston, Texas, set out to investigate how epithelial cells in the gut communicate with the immune system.

Activating immunity

The researchers found that colonizing mice with a specific strain of the commensal bacterium Escherichia coli, called 541-15, restored macrophages after antibiotic treatment. Mice with E. coli 541-15 were also protected against chemically induced colitis, showing less inflammation, longer colons, and lower disease markers than mice without the bacterium. 

E. coli 541-15, through its flagellin protein—which makes up the tail-like flagellum that the bacteria use to move, is sensed by a specific Toll-like receptor called TLR5 on epithelial cells that act like stem cells in the gut. These cells secrete molecules that attract immune cells, including macrophages. 

Using lab-grown “mini-colons” that mimic human intestinal tissue, the team discovered that mature colon cells did not respond to the bacteria, while the stem-like cells strongly activated genes involved in immune recruitment without causing inflammation. 

Microbial sensing 

Further experiments showed that E. coli 541-15 helps the colon recruit key immune cells that can develop into macrophages, leading to more mature, protective macrophages and fewer immature ones. 

This effect depended on a chemical signal called CCL2. When CCL2 was blocked or genetically removed from epithelial cells, mice were no longer protected against colitis, and fewer immune cells were recruited to the gut lining. E. coli strains with active flagellin activated TLR5 on epithelial cells, while strains without active flagellin didn’t.

It’s still unclear how these findings apply to humans, and whether other microbial signals help recruit immune cells to the gut, the authors say. However, they add, “our study demonstrates a role for intestinal epithelial stem cells in microbial sensing, which promotes intestinal macrophage replenishment and maturation and supports intestinal barrier function.”

The findings, published in Cell Reports, point to new avenues for preventing and treating the condition.

Although genetics play a role, obesity is mainly driven by lifestyle changes, including reduced physical activity and diets rich in highly processed foods. The gut microbiota is known to influence obesity, and emerging evidence suggests that people with obesity have less diverse and more inflammatory oral bacteria. But it is unclear whether and how oral bacteria may affect whole-body metabolism.

So, Ahmed Shibl at New York University Abu Dhabi in the United Arab Emirates and his colleagues analyzed data from the UAE Healthy Future Study, a project designed to understand factors that contribute to heart and metabolic diseases among Emirati adults.

Microbiota differences

The researchers analyzed data from 669 participants aged 18 to 43, collecting mouthwash samples, health measurements such as body weight, blood pressure, and cholesterol, and detailed lifestyle information, including smoking and exercise habits. 

By analyzing mouth bacteria, the team found that obesity was associated with distinct bacterial communities, lower microbial diversity, and increased levels of microbes linked to inflammation.

The researchers also found that many microbial pathways involved in breaking down sugars and generating obesity-related compounds were more active in obese people than in healthy-weight people.

Therapeutic strategies 

Compared to healthy-weight individuals, those with obesity had higher levels of molecules that are known to promote inflammation, interfere with insulin signaling, increase hunger, and raise the risk of diabetes and fatty liver disease. At the same time, people with obesity showed reduced microbial pathways responsible for making essential B vitamins, which are important for healthy energy use.

Computer models combining oral bacteria, their metabolic functions, and saliva chemicals could better distinguish obese from healthy individuals compared with clinical measurements alone. 

These results indicate a potential role of mouth bacteria in obesity-related diseases, the authors say. The findings, they add, “also suggest opportunities for microbiome-based prevention and therapeutic strategies against obesity and underscore the importance of investigating the oral microbiome’s contributions to other complex diseases.”

The findings, published in Cell Reports Medicine, suggest that specific gut microbes and metabolites can serve as biomarkers to help diagnosing depression and guide treatment.

While it’s known that certain microbes and metabolites can influence depression by affecting brain pathways and neurotransmitters, it’s unclear whether they could reliably help diagnose the condition.

Researchers led by Mingliang Zhao at Shanghai Jiao Tong University School of Medicine in China conducted a study analyzing gut bacteria and blood metabolites in dozens of people with depression, before and after treatment.

Metabolic patterns

By comparing blood and stool samples from non-depressed individuals with samples from people with depression, the researchers found that people with depression showed alterations in their blood metabolites. An analysis of more than 200 metabolites revealed 34 molecules that differed between depressed and non-depressed people.

Many of these changes were reversed after treatment, showing that medications can restore certain metabolic patterns. Animal experiments confirmed similar trends, supporting the connection between gut microbes, metabolism, and depression.

Using data from one group of participants, the researchers found that certain metabolites mediate the effects of specific gut microbes on depression. For example, the amino acid L-tyrosine mediated some of the effects of one bacterial species on depression, and homovanillic acid partly mediated the effects of another. 

Identifying depression

Key bacteria and metabolites, such as Bifidobacterium longum, Roseburia intestinalis, serotonin, and homovanillic acid, were linked to lower depression risk, while others, such as Blautia obeum and 2-hydroxybutyric acid, were linked to higher risk, the researchers found. 

Building on these findings, the team developed a machine-learning model using 34 metabolites that could reliably identify depressed individuals.

Although more research is needed to confirm these results, the findings “highlight metabolites as key mediators linking microbiota to depression and as valuable indicators for its identification,” the authors say.

In this interview, professor Piergiorgio Natali (Mediterranean Task force for Cancer Control) discusses the importance of improving functional foods as a strategy to support health, particularly during aging. In this context, special attention was given to whole tomato as a candidate food source because of its global availability, growing market relevance, and rich content of health-promoting nutrients with well-recognized anti-inflammatory potential.

The research line presented focuses on the development of a physical treatment process applied to the whole tomato, including peels and seeds, in order to obtain a powder with enhanced antioxidant and anti-inflammatory activity. According to the evidence collected so far, this formulation appears capable of inhibiting several biological pathways involved in chronic diseases. Supporting data have been generated across different levels of investigation, including laboratory studies, animal models, and human studies, providing a solid scientific basis for further development.

Tomato also offers an important advantage for clinical research, as the distribution of its major nutrients in the body is already well understood. This makes it possible to identify specific target organs that may benefit from the new formulation, including the liver, testis, and prostate. Beyond its direct biological activity, tomato may also exert beneficial effects on the intestinal microbiome by reducing inflammatory status and improving gut barrier permeability. Altogether, these findings support the potential of a whole-tomato–based functional formulation as an accessible and promising tool for the prevention or modulation of chronic disease-related processes and for the promotion of healthier aging.

The findings, published in Stem Cell Reports, suggest that argeting the gut microbiota could help improve gut repair in aging or disease.

Intestinal stem cells produce new cells that eventually become the various specialized cells of the gut. Aging not only reduces the function of these stem cells, it also alters the intestinal microbiota, which can contribute to digestive problems and other conditions. However, the exact interactions between gut microbes and stem cell aging are not yet fully understood.

To address this question, researchers led by Kodandaramireddy Nalapareddy at the University of Cincinnati in Ohio altered the microbiota of mice using antibiotics and fecal transplants between young and aged animals.

Boosting regeneration

Gut microbes are known to control a key signaling system called Wnt, which helps intestinal stem cells maintain and repair the gut lining. When mice were treated with antibiotics or raised without any gut microbes, Wnt signaling decreased. 

Transferring gut microbes from young mice into older animals boosted Wnt signaling and improved the function of intestinal stem cells. When aged mice received fecal transplants from young mice, their stem cells showed stronger activity, more cell division, and better regeneration after damage.

Instead, transferring gut microbes from old mice into younger animals had only a small effect on signaling and regeneration, the researchers found. 

Rejuvenating cells

In mice, certain microbes that become more common in aged intestines, such as Akkermansia muciniphila, were able to reduce Wnt signaling in intestinal stem cells and impair their regenerative function. This effect also involved changes in other microbial species that interact with A. muciniphila. 

The findings indicate that a youthful microbiota can boost the regenerative function of aged stem cells, but the exact interactions between microbes and intestinal stem cells need more research, the authors say.

“Our data imply potential therapeutic approaches via modulation of the composition of microbiota for aging-associated changes in the function of [intestinal stem cells].”

The findings, published in Nature Medicine, suggest that the therapy is safe and effective at reducing recurrence of C. difficile infection.

Previous studies using fecal microbiota transplants and microbiota-based therapies suggest that restoring gut bacteria could prevent recurrent C. difficile infection. In particular, VOS—an FDA-approved oral microbiota therapy, made of purified Firmicutes spores from healthy donors—has been shown to reduce infection risk compared to traditional fecal transplants. 

However, it’s unclear which specific bacterial species or metabolites are most important, and how VOS prevents recurrent C. difficile infection at a mechanistic level. So, Jessica Bryant at Seres Therapeutics in Cambridge, Massachusetts, and her colleagues conducted a clinical trial testing VOS in people with recurrent C. difficile infection.

Restoring the microbiota

The researchers gave either VOS bacteria or a placebo to 182 people who had recently taken the antibiotic vancomycin and had at least three C. difficile infection. Stool samples were collected before and after treatment to track how VOS bacteria colonized the gut.

Compared with people receiving the placebo, those who received VOS had more beneficial bacterial species appear in their guts, with more protective Firmicutes and fewer Proteobacteria and other disease-associated species. These bacteria stayed in the participants’ guts for at least 24 weeks, the researchers found.

In contrast, people on the placebo had slower and incomplete microbiota recovery, with fewer beneficial bacteria and more harmful species persisting in their guts. Participants who received VOS did not report significant side effects compared to those receiving the placebo.

Preventing recurrence

Before VOS treatment, participants had high levels of primary bile acids and low levels of protective secondary bile acids, a pattern that favors C. difficile growth. After VOS treatment, secondary bile acids and beneficial fatty acids increased rapidly, while primary bile acids decreased. 

Laboratory tests confirmed that these fatty acids can slow or stop C. difficile growth. Similar changes were also produced by VOS bacterial spores outside the body, suggesting that the treatment restores gut metabolites that help block infection, the authors say.“These data support a potential role for VOS, after antibiotic therapy, to restore the microbe-associated metabolic functions needed to prevent [C. difficile infection] recurrence.”

The findings, published in Cell Host & Microbe, suggest that specific microbial genes can affect how diet affects cancer progression.

Scientists have known that gut bacteria consume nutrients and produce metabolites that shape host physiology, and that dietary supplements can have mixed or even opposite effects in different individuals. However, it’s not known how specific microbial genes control nutrient availability inside tumors, nor how these genes interact with diet to influence immune cells and tumor outcomes. 

Working in mice, Shanshan Qiao at Cornell University in New York and her colleagues tested whether gut bacteria change how dietary amino acids influence cancer growth. 

Promoting cancer

The researchers compared mice with gut microbes to mice that lacked them and fed both groups diets with either low or high amino acid content. In mice without gut microbes, diets rich in amino acids led to higher amino acid levels in the body and faster tumor growth, but this effect was much weaker in mice with normal gut bacteria.

Human gut bacteria vary widely in how much they consume amino acids, and when these bacteria were transferred into mice, those receiving microbes that consumed more amino acids ended up with lower amino acid levels in their bodies. These animals also developed smaller tumors. 

Next, the researchers studied individual bacterial genes that break down amino acids in the gut and found that when these genes were missing, more amino acids remained available in the body and within tumors, promoting their growth. 

Precision medicine 

The team focused on a bacterial gene, called bo-ansB, that breaks down the amino acid asparagine. When bacteria were able to use asparagine, amino acid supplements worsened tumors, but when the bacteria could not use asparagine, the supplements improved tumor control by supporting cancer-fighting immune cells.

When bo-ansB was removed, more asparagine reached tumors, boosting immune responses and improving the effectiveness of anti-cancer therapy, the researchers found.

The findings suggest that gut microbes can influence cancer outcomes by regulating nutrient availability and uptake in immune cells, the authors say. The results, they add, “establish the gut microbiome as a genetically tractable ‘metabolic organ’ and uncover a regulatory layer linking dietary amino acid, microbiota function, and cancer—offering opportunities for precision medicine.”