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 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.”

Now, in a Commentary published in Med, Emily Hoedt and Nicholas Talley at the University of Newcastle in Callaghan, Australia, argue that effective treatment of IBD requires an approach combining tailored donors, microbiota analysis, and diet. “To move forward, we must embrace a more nuanced, personalized approach,” they say.

Because disruptions to gut microbes are common in conditions such as IBD, including ulcerative colitis and Crohn’s disease, therapies aimed at restoring the microbiota have gained increasing attention. Fecal microbiota transplants have shown promise, particularly in ulcerative colitis, but responses remain variable, and success appears to depend on donor characteristics. 

Diet, especially fiber intake, is thought to support microbial recovery, yet clinical results are inconsistent. While certain fibers can promote beneficial bacteria such as Faecalibacterium prausnitzii, many patients do not to improve or even experience worse symptoms. 

These mixed outcomes suggest that microbial presence alone may not be sufficient for treating disease, and that the functional capacity of the gut microbiota—such as the ability to degrade dietary fiber—may be critical, the authors say. However, they add, “mechanistic understandings of how food components influence disease activity are limited.”

Microbial function

Recent studies suggest that successful microbiota-based therapies depend not only on introducing beneficial microbes, but also on restoring microbial function. Fiber supplements, rather than improving outcomes for all patients, may have counterproductive effects if the recipient’s microbiota lacks the enzymes needed to degrade it or converts it into inflammatory metabolites.

The authors emphasize that beneficial clinical effects arise when engrafted microbes actively produce protective metabolites—such as short-chain fatty acids—and interact appropriately with the host’s immune system. This suggests that matching donors and recipients is important.

Beyond bacteria, also fungi and viruses may influence outcomes, indicating that microbial composition alone is less important than microbial functionality and host-microbe interactions for therapeutic success.

Lasting remission 

Supporting beneficial microbes while limiting inflammation can improve the effectiveness of microbiota-based therapies, the authors say. In the future, they add, larger studies will be essential to identify responders and guide precision nutrition.

Hoedt and Talley conclude that microbiota-based therapies such as fecal microbiota transplants cannot be optimized through a one-size-fits-all approach. Long-term remission in IBD and related conditions likely relies on personalized strategies combining donor selection, microbiota profiling, and tailored diet, the authors say.

“This will require interdisciplinary collaboration across microbiology, nutrition, immunology, and clinical medicine,” they add. “Only then can we unlock the full potential of microbiome-based therapies and achieve lasting remission for patients with chronic gastrointestinal diseases.”

The findings, published in Science Immunology, suggest that gut Clostridia can be divided into two groups, with one group contributing to gut inflammation under certain conditions.

Scientists have known that Clostridia bacteria make proteins called flagellins, which build flagella. Flagellins can also interact with the immune system, with some triggering only weak immune responses and others causing inflammation. However, it’s unclear how differences in flagellin types affect their ability to stimulate the immune system and which flagellins promote or prevent inflammation in the gut.

To address this question, Lennard Duck at the University of Alabama at Birmingham and his colleagues set out to study more than 100,000 bacterial genomes from gut Clostridia.

Immune activation

The researchers found that the genes controlling flagella, called motility genes, are arranged differently across Clostridia bacteria, even among closely related families. Some bacteria, such as Lachnospiraceae, have multiple motility genes and more diverse flagellins, while others have fewer of these genes and less diversity. 

Based on flagellin diversity and motility gene organization, the team classified gut Clostridia into two groups, G1 and G2. Next, they tested these two groups of bacteria in germ-free mice to see how they affect the gut. 

Both groups could colonize the gut, boost protective immune cells, and stimulate the production of antibodies that help maintain normal gut balance. However, G2 bacteria triggered stronger responses in gut cells, including genes linked to inflammation and stress, while G1 bacteria mainly activated protective functions. 

Gut inflammation 

When the gut’s barrier was weakened, G2 bacteria—but not G1 bacteria—caused inflammation and tissue damage in the colon lining. The researchers found that flagellins differ between G1 and G2 gut bacteria: Most G1 bacteria produce flagellins at very low levels, while G2 bacteria produce flagellins that strongly activate the immune system. What’s more, G2 flagellins stimulate inflammatory signals, whereas G1 flagellins don’t. 

In people with Crohn’s disease, G1 bacteria are typically reduced, while G2 bacteria are more abundant in inflamed tissues, the researchers also found. This finding, they say, suggests that the balance between G1 and G2 bacteria and their flagellins may influence gut inflammation and disease. 

“This study identified key features of specific commensal bacteria that have colitogenic potential and revealed one mechanism whereby these organisms can potentially initiate intestinal inflammation,” the authors say.

Although attempts to modulate or manipulate the intestinal microbiome have so far yielded limited and not entirely satisfactory clinical results, this may largely reflect the remarkable complexity of the gut microbial ecosystem and the fact that many of its mechanisms remain poorly understood. In this context, Vecchi also presented findings from a study in patients with mild to moderate active ulcerative colitis treated either with mesalazine alone or mesalazine plus Lactobacillus rhamnosus GG. While the addition of the probiotic did not produce statistically significant differences in clinical endpoints, it was associated with immunoregulatory effects on the mucosal immune system and with a reduction in fecal calprotectin, a key marker of intestinal inflammation. 

These findings suggest that microbiome-based adjunctive strategies, when combined with standard therapy, may offer benefits particularly in supporting long-term disease control and maintenance of remission.

The findings, published in Cell Host & Microbe, suggest that targeted dietary strategies could be used to reduce susceptibility to cholera.

Studies have shown that diet influences the gut microbiota and some milk-derived proteins can inhibit cholera toxin activity. However, how specific dietary components affect V. cholerae metabolism and virulence, as well as its interactions with commensal gut bacteria, remains unclear.

Researchers led by Rui Liu at the University of California, Riverside used adult mice to test how different diets affect V. cholerae infection.

Protective diets

The researchers fed mice diets high in carbohydrate, fat, or protein, including protein from casein, soy, or wheat, and then infected the animals with V. cholerae after reducing the mice’s gut microbiota with antibiotics. 

Mice on high-protein diets with casein or wheat protein had much lower levels of V. cholerae colonization compared with mice on high-carbohydrate, high-fat, or soy-protein diets.

V. cholerae in mice fed casein or wheat protein appeared to alter the activity of many genes, reducing some involved in metabolism and virulence. Diets with soy protein did not trigger these changes.

Diet-driven outcomes 

Further experiments revealed that one V. cholerae’s gene, called flrA, is linked to diet-induced changes in metabolism, virulence, and a molecular “weapon” that V. cholerae uses to compete with gut microbes.

Disabling flrA restored bacterial growth and the ability of the bacterium to compete with the resident microbiota, the researchers found.The findings highlight how diet and microbial interactions together may influence the outcome of V. cholerae infection. However, the authors say, “the complexity of actual human diets and microbiota means that the range of potential diet-driven outcomes of V. cholerae colonization or infection is vast and will require much additional study to fully elucidate.”

Franceschi highlights that quantitative and qualitative disruptions of the microbial ecosystem (dysbiosis) can negatively affect immune function, with diet acting as a key modifier: a carbohydrate-heavy, protein-poor pattern may impair antibody-related responses and promote metabolic conditions such as diabetes, which are linked to immune dysfunction and higher infection susceptibility. The interview then focuses on bacterial translocation across a compromised intestinal barrier as a plausible pathway contributing to sepsis. Data from the group’s research indicate that patients with sepsis or septic shock display a distinctly dysbiotic microbiota compared with healthy controls, suggesting that microbial signatures may accompany—or potentially shape—critical illness trajectories. 

Finally, Franceschi reviews preclinical studies investigating probiotic-based strategies (including metabolically relevant bacteria) alongside antibiotics: in animal models, probiotic pre-treatment and continuation during antibiotic therapy have been associated with improved survival compared with antibiotics alone. These findings are encouraging but remain preliminary, underscoring the need for well-designed human trials to assess translatability and clinical impact on sepsis outcomes and mortality.

The findings, published in Cell Host & Microbe, suggest that these bacteria must be used with caution in probiotics and microbiota-based therapies.

Before this study, not much was known about whether lantibiotic-producing bacteria influence the recolonization of the gut microbiota, how they impact beneficial bacteria, and whether interventions such as fecal transplants could restore microbiota diversity in their presence.

So, Cody Cole at the University of Chicago in Illinois and his colleagues studied how a lantibiotic-producing gut bacterium called BpSCSK affects gut recovery after antibiotic treatment.

Dominating the microbiota

In mice with a full gut microbiota, BpSCSK could not establish itself in the intestine. However, after antibiotics, which reduced resident bacteria, BpSCSK successfully colonized the gut and became the dominant species. 

BpSCSK also prevented gut bacteria, including those that produce beneficial compounds such as short-chain fatty acids, from returning. For weeks after colonization with BpSCSK, mice had lower gut bacterial diversity and decreased levels of beneficial metabolites such as butyrate. 

Even when the researchers tried to restore the gut microbiota with a fecal transplant from healthy mice, BpSCSK continued to be dominant, preventing many other bacteria from colonizing the gut. 

Infection susceptibility

Mice colonized with BpSCSK after antibiotics became more vulnerable to infections with opportunistic pathogens such as Klebsiella pneumoniae and Clostridioides difficile, showing weight loss and metabolic changes that favor pathogen growth. 

However, when the animals were exposed to a microbiota that had previously developed with BpSCSK, this community of bacteria successfully colonized the gut, reducing BpSCSK’s dominance. In these mice, microbial diversity was restored and the levels of beneficial metabolites grew, the researchers found.

The findings suggest that lantibiotic-producing bacteria can have a detrimental role in microbiota diversity and function, the authors say. “More work is needed to determine the therapeutic potential of lantibiotics and to better characterize the novel lantibiotics currently found in probiotics and microbiomes to mitigate off-target side effects that could impair commensal bacterial functions.”