Mucosal glycans: key drivers of the development of inflammatory bowel disease and a potential new therapeutic target - Nature Reviews Gastroenterology & Hepatology

Une découverte inattendue sur notre immunité ?
Des chercheurs japonais révèlent un rôle peu exploré de la salive.

📌 Ce qu’il faut savoir
Une équipe de l’Université de Tokyo a analysé la salive de 476 volontaires.
Leurs travaux, publiés dans Nature Communications, identifient des fragments génétiques jusqu’ici peu décrits, portés par certaines bactéries de la bouche.

➡️ Ces fragments, appelés Inocles, sont présents chez près de 3 personnes sur 4.
Il s’agit de petits morceaux d’ADN supplémentaires, distincts de l’ADN principal des bactéries.

Ils ne sont pas indispensables à leur survie, mais semblent leur conférer des capacités d’adaptation accrues, notamment pour faire face aux contraintes constantes de l’environnement buccal (alimentation, acidité, hygiène…).

👉 Pourquoi est-ce important ?
Parce que la bouche n’est pas qu’un simple point de passage. C’est un écosystème biologique dense et actif, où :
-un microbiote complexe cohabite en permanence
-certaines bactéries interagissent avec notre organisme
-ces interactions pourraient être associées à des variations de la réponse immunitaire

Ce que les chercheurs ont observé chez les personnes porteuses d’Inocles :
-une activité immunitaire différente
-notamment au niveau de cellules clés de l’immunité adaptative
Autrement dit, ce qui se passe dans la bouche pourrait influencer la manière dont notre système immunitaire se régule.

Quels liens ont-ils fait avec le cancer ?
Les chercheurs ont également observé que certaines personnes atteintes de certains cancers présentaient moins d’Inocles.
Il ne s’agit ni d’un lien causal, ni d’un traitement, mais d’une piste de recherche encore très précoce.

⚠️ À ce stade, ces résultats sont observationnels. Ils ouvrent de nouvelles questions, mais nécessitent encore de nombreuses études pour être confirmés. | 37 comments on LinkedIn

Head and neck #cancer is the seventh most common cancer worldwide.

This JAMA Review summarizes the epidemiology, clinical presentation, diagnosis, and treatment of head and neck squamous cell carcinomas (#HNSCC) of the upper aerodigestive tract.

https://ja.ma/4q6rxjn

Just as a curiosity.
"Chris Buck stands barefoot in his kitchen holding a glass bottle of unfiltered Lithuanian farmhouse ale. He swirls the bottle gently to stir up a fingerbreadth blanket of yeast and pours the turbulent beer into a glass mug.

Buck raises the mug and sips. “Cloudy beer. Delightful!”

He has just consumed what may be the world’s first vaccine delivered in a beer. It could be the first small sip toward making vaccines more palatable and accessible to people around the world. Or it could fuel concerns about the safety and effectiveness of vaccines. Or the idea may go nowhere. No matter the outcome, the story of Buck’s unconventional approach illustrates the legal, ethical, moral, scientific and social challenges involved in developing potentially life-saving vaccines."
https://lnkd.in/gdPZRTsV

We are proud to share newly published work from the Sjögren’s Foundation led by Foundation authors Kristie Cox, PhD and Matt Makara, MPH, now available in the Journal of Dental Research.
 
This review examines the connection between oral pathology and systemic disease in Sjögren’s disease, the current challenges in diagnosis and treatment, and the importance of integrated models of care that address both oral and systemic manifestations.
 
Highlights from the publication:
• A strong connection between oral pathology and systemic disease, including neuropathies, exists with Sjögren’s disease
• Current diagnostic and treatment paradigms are insufficient and there is a need for advanced and integrated approaches
• A multidisciplinary and patient centered model may improve outcomes and quality of life
 
Read the abstract:
https://lnkd.in/e2iBfjcg

See Figure 1 from the article on Salivary Gland Pathophysiology:
https://lnkd.in/eQaQUSjD

𝗡𝗲𝘄 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵: 𝗧 𝗰𝗲𝗹𝗹𝘀 𝗶𝗻 𝘁𝗶𝘀𝘀𝘂𝗲𝘀 𝗱𝗶𝗳𝗳𝗲𝗿 𝗺𝗮𝗿𝗸𝗲𝗱𝗹𝘆 𝗳𝗿𝗼𝗺 𝘁𝗵𝗼𝘀𝗲 𝗶𝗻 𝗯𝗹𝗼𝗼𝗱 - 𝗿𝗲𝘀𝗵𝗮𝗽𝗶𝗻𝗴 𝗵𝗼𝘄 𝘄𝗲 𝗲𝘃𝗮𝗹𝘂𝗮𝘁𝗲 𝘃𝗮𝗰𝗰𝗶𝗻𝗲𝘀 𝗮𝗻𝗱 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝗶𝗲𝘀

A new study in Immunity from Washington University School of Medicine in St. Louis reveals that #Tcells residing in tissues such as the #tonsils differ significantly from T cells circulating in the #blood. This challenges long-standing assumptions in #immunology and could transform how we assess immune responses to #vaccines, #infections, and #immunotherapies.

In one of the largest single-cell datasets of human T cells ever generated, researchers analyzed 5.7 million T cells from paired tonsil tissue and blood samples of 10 donors. Led by Dr. Naresha Saligrama, the team found profound differences in T cell subtypes and functions between compartments even within the same individual.

Why does this matter?

▪️ Less than 2% of the body’s T cells are actually in the blood, yet blood is currently the standard sample type used for immune monitoring.
▪️Many specialized T cells - including resident memory T cells and T follicular helper cells - exist almost exclusively in tissues, not blood.
▪️Tissue location can shape a T cell’s phenotype and its ability to recognize specific antigens.

🔍 Significance

This study highlights the need for a more tissue-aware approach to evaluating immune responses. Relying solely on blood samples may overlook critical populations of T cells that drive protection, disease progression, or therapeutic responses. Future vaccine design, #immunotherapy evaluation, and clinical diagnostics may need to incorporate location-specific immune profiling to truly understand human #immunity.

🗃️ See comments section for reference.

A toxin-secreting gut bacterium may fuel ulcerative colitis by killing protective immune cells that maintain intestinal homeostasis, according to a new study in Science.

The findings suggest potential for new treatment strategies.

📄: https://scim.ag/4oXOowT
#SciencePerspective: https://scim.ag/4a69oN6

The appendix is a small, worm-like diverticulum of the caecum, potentially having a role in regulating intestinal microbiota and immunology. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. The pathophysiology of appendicitis is still poorly understood. During the past decade, evidence has overturned the long-lasting dogma that all appendicitis cases have a clinical course inevitably progressing to perforation and life-threatening peritonitis unless operated upon in a timely manner. Instead, this natural course occurs only in a smaller proportion of patients, for whom emergency appendectomy remains mandatory. Advances in diagnostic accuracy following utilization of clinical scoring systems and imaging has enabled more accurate pre-interventional assessment of appendicitis disease severity. While some patients still require urgent surgery, the majority can be treated successfully with antibiotics, and in some the disease has even been shown to resolve spontaneously. This has confirmed the notion of at least two different forms of appendicitis: non-perforating and perforating, often referred to as uncomplicated and complicated appendicitis. Unified definitions of these forms are still undergoing rigorous research and debate, hampering both comparison of different studies and the establishment of unified treatment guidelines. The current knowledge on the safe and effective outcomes of non-operative treatment alternatives has further underlined the need for standardized uniform definitions of appendicitis severity and assessment of the success of two fundamentally different treatment options. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. In this Primer, Salminen and colleagues review the epidemiology, pathophysiology, diagnosis and management of appendicitis, and discuss future research areas.

Advances and prospects of respiratory mucosal vaccines: mechanisms, technologies, and clinical applications - npj Vaccines

I thought a banana was loaded with chemicals.

That’s until I found the ingredient list for human breast milk.

If you saw this list on a label, you might think it’s never been anywhere near a human.

And if you go by how they’re pronounced— you might be ready to starve an infant.

Good thing we don’t have anyone silly enough to believe that these chemicals are a bad thing…

——-

HUMAN MILK INGREDIENT LIST: Water, lactose, triacylglycerols [oleic acid, palmitic acid, linoleic acid, alpha-linolenic acid, stearic acid, lauric acid, myristic acid], phospholipids [sphingomyelin, phosphatidylcholine], cholesterol, free fatty acids [docosahexaenoic acid (DHA), arachidonic acid (ARA)]),

Oligosaccharides (2′-fucosyllactose, lacto-N-tetraose, lacto-N-neotetraose, 3′-sialyllactose, 6′-sialyllactose, fucosylated and sialylated oligosaccharides),

Milk Proteins (α-lactalbumin, lactoferrin, secretory immunoglobulin A, serum albumin, lysozyme, β-casein),

Minerals (potassium, calcium, chloride, phosphorus, sodium, magnesium, iron, zinc, iodine, copper, selenium, manganese),

Free Amino Acids (glutamic acid, glutamine, taurine, alanine, glycine, serine, threonine, valine, leucine, isoleucine, lysine, methionine, phenylalanine, tyrosine, tryptophan, cysteine, histidine),

Vitamins (vitamin A [retinol], vitamin D, vitamin E [α-tocopherol], vitamin K, vitamin C [ascorbic acid], thiamin [B1], riboflavin [B2], niacin [B3], pantothenic acid [B5], vitamin B6, folate [B9], vitamin B12),

Enzymes (bile salt–stimulated lipase, amylase, proteases),

Proprietary Blend (nucleotides, choline, phosphocholine, carnitine, inositol, polyamines),

Hormones & Growth Factor Blend (insulin, leptin, adiponectin, epidermal growth factor, insulin-like growth factor-1, transforming growth factor-β),

Cytokines & Immune Factor Blend (MicroRNAs, Living Cells (leukocytes, epithelial cells, stem-like cells)).

—-

#mammals #foodchemistry #foodscience #humanchemicalfactories #sciencerules | 80 comments on LinkedIn

Efficacy, Immunogenicity, and Safety of the Live-Attenuated Intranasal Pertussis Vaccine BPZE1: A Randomised, Placebo-Controlled Phase 2b Human Challenge Study in the UK:

The resurgence of pertussis is largely attributed to suboptimal vaccination coverage, particularly in countries that rely exclusively on acellular vaccines, which fail to induce mucosal immunity and generate minimal indirect (herd) protection. Consequently, sustained coverage levels above 95% are required to control transmission. BPZE1 is a live-attenuated Bordetella pertussis strain developed for intranasal administration, engineered through the genetic inactivation or deletion of three key virulence factors—pertussis toxin (PT), dermonecrotic toxin (DNT), and tracheal cytotoxin (TCT)—to safely prevent whooping cough while closely mimicking natural infection. This vaccine elicits robust Th1-biased cellular immunity alongside strong humoral responses. In a phase 2b human challenge study, intranasal BPZE1 vaccination prevented or markedly reduced infection following exposure to virulent B. pertussis, supporting its potential as a promising next-generation pertussis vaccine. Given its favorable safety profile, large-scale phase 3 clinical trials are warranted to confirm these findings and further assess its public health impact.

#pertussis
#pertussisvaccines
#mucosalvaccines
#nasalvaccines


https://lnkd.in/gukzy-aE

A mother's touch: microbial guardians of early immune imprinting
Trends in Immunology, Month 2025, Vol. xx, No. xx https://lnkd.in/gJuDgB4B

Group 3 Innate Lymphoid Cells (ILC3s) are a firmly established and universally accepted concept in immunology. They are considered the "innate counterparts" to T helper 17 (Th17) cells, as both share the master transcription factor, Retinoid-Related Orphan Receptor gamma t, and produce the cytokines IL-17 and IL-22.
This review:
·      The Biological Paradigm: Infants are born with a pre-established "immune memory" despite developing in a relatively sterile environment. This in utero priming is driven by the maternal immune system and microbiota through a multi-modal exchange involving maternal microchimeric cells, IgG transfer, and microbiota-derived metabolites/antigens.
·      Mechanisms of Action: Recent murine and human data demonstrate that maternal microbial products cross the placental barrier to actively fine-tune the fetal immune system. This results in antigen-specific immunological memory and epigenetic imprinting, effectively "programming" fetal immune cells before birth.
·      Clinical Significance: This delicate priming process is highly susceptible to external stressors. Maternal dysbiosis, driven by diet, antibiotics, or infection, can disrupt these pathways, leading to aberrant immune development. Such prenatal perturbations are increasingly linked to the pathogenesis of autoimmune and immune-mediated disorders later in life.

Figure: Maternal factors that shape fetal immune priming.
During gestation, microbial and dietary antigens are trafficked across the placenta, partially via neonatal Fc receptor (FcRn)-mediated transport of immune complexes. These antigens are taken up by fetal dendritic cells (DCs) for priming of T cells, which are predisposed to differentiate into regulatory T cells (Tregs), thus establishing a level of immune tolerance toward commensals and dietary antigens before birth. Microbiota-associated metabolites, such as short-chain fatty acids (SCFAs) and tryptophan (Trp) derivatives, also cross the placenta and contribute to Treg priming, while maternal microchimeric cells take up residence in fetal tissues and promote tolerance of maternal antigens. Maternal interleukin (IL)-10 further promotes a tolerogenic immune milieu in the fetus, while, in situations of maternal immune activation (MIA), cytokines, such as IL-6 and IL-17, may skew newly activated T cells toward a more inflammatory profile, and alter the development of the intestinal epithelium and central nervous system. Dotted lines indicate pathways that are speculative.

The concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barriers and that this fundamental task can be directly or indirectly regulated by immune cells. Indeed, several types of leukocytes can help build protective barriers when required, potentially either by depositing matrix components themselves in certain circumstances or, more generally, by interactions with canonical structural cells and the existing extracellular matrix. This concept of structural functions of immune cells challenges the rigidity with which mammalian tissue organization and immune defence have been traditionally compartmentalized. Although there is strong momentum in the evidence for structural immunity that has been acquired so far, the field lacks a comprehensive overview of these data as well as a critical evaluation of this concept. Here, we place independent findings from several groups into a working model of immune cells as the architects of tissue barriers, to present a framework on which new concepts and findings in this area can develop. This Perspective presents a framework of ‘structural immunity’ that positions immune cells as architects of tissue structure. Beyond their roles in antimicrobial defence, we posit that immune cells contribute to tissue homeostasis by guiding structural composition and, in some cases, directly building barrier components.

⚘️En 2008, la biologiste Katie Hinde a découvert quelque chose que la science avait ignoré pendant des siècles : le lait maternel n’est pas une recette fixe, c’est un message en perpétuel changement.

En étudiant des macaques en Californie, Hinde remarqua un motif étrange. Si la mère avait un petit mâle, son lait était plus épais, riche en graisses et en protéines (un carburant à haut indice d’octane). Si elle avait une petite femelle, le lait était plus abondant et chargé en calcium. Comment le corps de la mère savait-il modifier la formule chimique selon le sexe du bébé ?

Cela l’a conduite à découvrir le mécanisme le plus fascinant de la biologie humaine : le « flux rétrograde ».

Pendant des années, nous avons cru que le lait allait dans une seule direction (de la mère à l’enfant). Nous avions tort. Lorsqu’un bébé tète, le vide créé aspire une petite quantité de salive du bébé à l’intérieur du mamelon de la mère.
C’est là que se produit la magie : le tissu mammaire analyse cette salive. C’est un scanner biologique.

Si la salive contient des signaux indiquant que le bébé a de la fièvre ou une infection, le corps de la mère commence à fabriquer des anticorps spécifiques à cette maladie en quelques heures.

Si le bébé est stressé, le lait modifie ses niveaux hormonaux (comme le cortisol) pour influencer son tempérament.
Le lait change entre le matin et le soir. Il change si le bébé est malade. Il change selon qu’il est garçon ou fille.

Comme l’a conclu Hinde : « Le lait maternel est nourriture, médicament et signal ». C’est le système de communication le plus sophistiqué de la nature, une conversation silencieuse entre deux corps que même la technologie moderne n’a pas encore réussi à reproduire entièrement.

Validation historique et scientifique, Katie Hinde, PhD – Laboratoire de lactation comparée, Arizona State University.

vanhille.fr | 100 comments on LinkedIn

Gut Phageome: A New Frontier for Clinicians

A new Nature study using long-read metagenomics reveals that the human gut microbiome is far more dynamic than we thought

https://lnkd.in/dnVnetzX

Most gut bacteriophages (phages) are integrated in bacterial genomes, but a meaningful fraction are gained, lost, or even jump across bacterial species over time.

This means the gut microbiome is not just a community of bacteria - it’s an evolving genetic ecosystem shaped by phage–bacteria interactions.

Why it matters for clinical practice

Emerging evidence suggests that phage dynamics can influence:

• microbiome stability and dysbiosis
• inflammation and immune tone
• responses to antibiotics, diet, and microbiome-targeted therapies

Phage-aware diagnostics and therapeutics (including targeted phage cocktails) are already entering early clinical and translational research.

Take-home for clinicians:

1. The virome matters: Gut phages may become essential in interpreting microbiome results and understanding dysbiosis.

2. Therapies will evolve: Next-generation probiotics, FMT, and phage therapy will likely consider phage–bacteria interactions.

3. Expect personalization: Phage patterns may soon help stratify patients and guide individualized microbiome interventions.

Understanding the phageome is becoming a key part of understanding our gut

I believe this is one of the most important papers in microbiome science.

This new review in Neuron (Mitchell et al, 2025) systematically dismantles the gut microbiome-autism hypothesis through a critical assessment of published papers.

I was honestly shocked by the numbers: Despite 100+ papers per year and $20-25M in annual NIH funding since 2018, the most cited studies have tiny sample sizes (n=20 for some), uncorrected multiple testing, and contradictory findings. Some report higher microbial diversity in autism, others lower, many find no difference. The taxa they report are inconsistent. When properly analyzed with sibling controls and adequate statistical power, associations largely disappear.

The mouse model data is equally troubling. For example, a 2019 Cell paper claimed fecal transplants from autistic donors induced "autism-like behaviors" in mice. But when reanalyzed with proper statistics, the effects vanished. And it is really not clear how mouse behavior can model human autism.

And these are not obscure papers - they are published in the most high profile journals and have thousands of citations each.

Maybe it is not surprising that randomized controlled trials of probiotics show no consistent benefit for autism.

As a result, we're watching well-intentioned science fuel a billion dollar "wellness" industry selling unproven interventions to vulnerable families.

As a microbiome scientist, this really troubles me. Excellent research IS being done, and the microbiome holds real promise as a diagnostic and therapeutic tool. But these overhyped, methodologically weak studies cast a shadow over our entire field.

The solution, in my opinion – and completely I agree with the authors on this – is to adopt the rigor that transformed human genomics: pre-specified hypotheses, adequate power, standardized protocols and pipelines, large sample sizes, statistical robustness, replication, and above all: resisting the hype machine.

#microbiome #autism #scientificrigor #reproducibility #clinicaltrials | 36 comments on LinkedIn

The Gram-negative bacterium Bordetella pertussis causes whooping cough (pertussis), a severe respiratory disease, especially in young children, which is resurgent despite high vaccine coverage. The current acellular pertussis vaccine prevents severe disease but does not prevent nasal infection with B. pertussis. This parenterally delivered vaccine induces potent circulating antibody responses but limited respiratory tissue-resident memory T cells and IgA responses. Here we developed a vaccine approach based on respiratory delivery of antibiotic-inactivated B. pertussis (AIBP). Ciprofloxacin-treated B. pertussis potently activated antigen-presenting cells to drive T cell responses. AIBP immunization via aerosol or intranasal administration conferred a high level of protection against lung and nasal infection. The AIBP vaccine induced B. pertussis-specific interleukin (IL)-17-producing CD4 tissue-resident memory T cells that recruited neutrophils to the respiratory tract. Protection was abrogated by depletion of CD4 T cells or neutralization of IL-17 in mice. Unlike a parenterally delivered whole-cell pertussis vaccine, which induced high levels of serum IL-1β, IL-6, tumour necrosis factor and C-reactive protein, aerosol immunization with the AIBP vaccine did not promote systemic pro-inflammatory responses. We present preclinical evidence of a safe and effective respiratory-delivered vaccine platform for inducing T cell-mediated sterilizing immunity against a respiratory pathogen. In this preclinical study, the authors find that respiratory immunization with an antibiotic-treated bacterial vaccine is a highly effective approach for inducing tissue-resident memory T cells that protect against lung and nasal infection with Bordetella pertussis.

A team of Trinity College Dublin researchers has developed a new form of vaccine that could transform how we are protected from respiratory infections and reduce the chance of passing on whooping cough.

It could mean a whooping cough vaccine, currently given by way of injection, could be administered nasally to children and young ­babies whose lives are more at risk from the disease.

The research was led by Prof Kingston Mills (pictured) and Dr Seyed Davoud Jazayeri from the college's School of Biochemistry and Immunology. “We’ve applied our understanding of protective immune pathways to engineer a fundamentally different kind of vaccine. By stimulating immunity where infections begin, we can offer stronger protection and potentially interrupt community transmission,” Prof Mills said

Whoopingcough can sound like an old fashioned disease but Ireland has had a resurgence in whooping cough, with a record 713 cases reported last year. More than one in four of those infected needed hospital treatment.

The landmark study, published in Nature Microbiology, found the experimental vaccine in pre-clinical studies managed complete protection against infection of the lungs and nasal cavity. The research was initially funded through a Research Ireland and is now advancing under the Arc Hub for Therapeutics.

Read a summary here: https://lnkd.in/e8XcN3RF

Read the full story here: https://lnkd.in/e_wnmS-E

IBS, Irritable Bowel Syndrome, is a common gastrointestinal disorder, more common, in women, with symptoms such as abdominal pain, constipation or diarrhea. The cause of the disease is not clear, but the intestinal environment including the gut microbiota and serotonin appear to be important...