Human milk oligosaccharides (HMOs) are bioactive components of breast milk with diverse health benefits, including shaping the gut microbiota, modulating the immune system, and protecting against infections. HMOs exhibit dynamic secretion patterns during lactation, influenced by maternal genetics and environmental factors. Their direct and indirect antimicrobial properties have garnered significant research interest. However, a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.

To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial, viral, and protozoal pathogens.

A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library focused on studies investigating natural and synthetic HMOs, their secretion dynamics, and antimicrobial properties. Studies involving human, animal, and in vitro models were included. Data on HMO composition, temporal secretion patterns, and mechanisms of antimicrobial action were extracted. Quality assessment was performed using validated tools appropriate for study design.

A total of 44 studies were included, encompassing human, animal, and in vitro research. HMOs exhibited dynamic secretion patterns, with 2′-fucosyllactose (2′-FL) and lacto-N-tetraose peaking in early lactation and declining over time, while 3-fucosyllactose (3-FL) increased during later stages. HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition, biofilm disruption, and enzymatic activity impairment. Synthetic HMOs, including bioengineered 2′-FL and 3-FL, were structurally and functionally comparable to natural HMOs, effectively inhibiting pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Campylobacter jejuni. Additionally, HMOs exhibited synergistic effects with antibiotics, enhancing their efficacy against resistant pathogens.

HMOs are vital in antimicrobial defense, supporting infant health by targeting various pathogens. Both natural and synthetic HMOs hold significant potential for therapeutic applications, particularly in infant nutrition and as adjuncts to antibiotics. Further research, including clinical trials, is essential to address gaps in knowledge, validate findings, and explore the broader applicability of HMOs in improving maternal and neonatal health.

• Human milk oligosaccharides
• Human milk oligosaccharides secretion dynamics
• Antimicrobial activity
• Breastfeeding
• Synthetic human milk oligosaccharides
• Pathogen adhesion inhibition
• Infant health

• barrier integrity and function
• gut microbiota
• immune regulation
• inflammatory response
• ischemic stroke
• microbiota-gut-brain axis
• microbiota-immune-barrier axis
• post-stroke depression

• Humans
• Gastrointestinal Microbiome/immunology
• Depression/immunology
• Depression/etiology
• Depression/microbiology
• Brain-Gut Axis/immunology
• Brain-Gut Axis/physiology
• Stroke/immunology
• Stroke/complications
• Stroke/microbiology
• Stroke/psychology
• Animals
• Immunomodulation

• Brain-gut axis
• Mood disorder
• bipolar disorder
• depression
• mental health
• microbiota
• psychiatry

• Humans
• Gastrointestinal Microbiome/physiology
• Brain-Gut Axis/physiology
• Mood Disorders/therapy
• Mood Disorders/physiopathology
• Fecal Microbiota Transplantation
• Bipolar Disorder/therapy
• Bipolar Disorder/physiopathology
• Bipolar Disorder/microbiology
• Prebiotics/administration & dosage

• cancer
• inflammation
• intestinal stem cells
• microbiome
• nutrients

• Animals
• Humans
• Gastrointestinal Microbiome
• Diet
• Drosophila melanogaster/microbiology
• Intestines/microbiology
• Stem Cells/metabolism
• Host Microbial Interactions
• Signal Transduction
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/metabolism

• Biomarker
• Colorectal cancer (CRC)
• Diagnostic
• Gut microbiota
• Host genetics
• Precision medicine
• Predictive
• Prognostic
• Treatment

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/microbiology
• Precision Medicine/methods
• Gastrointestinal Microbiome/genetics
• Biomarkers, Tumor/genetics
• Prognosis

• IL-10
• Lactobacillus
• aristolochic acid
• macrophage
• renal injury
• von Hippel–Lindau

• Crohn’s disease
• Periodontitis
• dysbiosis
• gum–gut axis
• immune response
• inflammatory bowel disease [IBD]
• oral bacteria
• oral–gut axis
• ulcerative colitis

• Humans
• Periodontitis/immunology
• Periodontitis/complications
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/physiopathology
• Inflammatory Bowel Diseases/immunology
• Gastrointestinal Microbiome/physiology
• Mouth/microbiology

• University of Maryland School of Dentistry
• R56 DK131277 NIDDK NIH HHS
• Johns Hopkins School of Medicine to C.L.S
• R03 DE029258 NIDCR NIH HHS
• R03DE029258 and R56DK131277 NIH HHS
• National Institutes of Health

• Age
• Enterocolitis
• Functional outcomes
• Hirschsprung’s disease

• Humans
• Hirschsprung Disease/surgery
• Hirschsprung Disease/complications
• Female
• Male
• Enterocolitis/etiology
• Enterocolitis/epidemiology
• Retrospective Studies
• Infant
• Quality of Life
• Child, Preschool
• Treatment Outcome
• Postoperative Complications/etiology
• Postoperative Complications/epidemiology
• Laparoscopy/methods
• Child
• Age Factors
• Time-to-Treatment

• NCRCCHD-2022-GP-04 National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University
• National Clinical Research Center for Child Health and Disorders, Children’s Hospital of Chongqing Medical University

• enzymatic cross-linking
• intestinal mucosal immunity
• mouse model
• soybean allergy
• tofu

• No. 31460439 National Natural Science Foundation of China
• No. 32260595 National Natural Science Foundation of China
• No. 20225BCJ22022 The Funding for Academic and Technical Leaders in Major Disciplines, Jiangxi Province, China

• Behavior
• D1R-expressing neurons
• Gut microbiota
• Striatum
• γδ T cells

• Animals
• Mice
• T-Lymphocytes
• Corpus Striatum
• Gastrointestinal Microbiome
• Neurons
• Compulsive Behavior
• Hippurates

• Gastrointestinal immune system
• barrier function
• degree of methylation
• dietary fiber
• pectin

• Pectins/chemistry
• Pectins/pharmacology
• Humans
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/physiology
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/drug effects
• Gastrointestinal Tract/microbiology
• Dietary Fiber/pharmacology
• Structure-Activity Relationship
• Immune System/drug effects
• Animals
• Methylation
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism

• conjunctiva
• cow
• histology
• lymphoid tissue
• mucosa

• FY2017-2019 Ito Foundation
• 19H03113 Japan Society for the Promotion of Science

• cancer
• microbiome
• prebiotics
• tumour

• Humans
• Prebiotics
• Inulin/pharmacology
• Diet
• Neoplasms/drug therapy

• cancer
• immunomodulation
• microbiota
• oncosuppressive
• prebiotics
• probiotics

• Alkaline Phosphatase
• Cytokines
• Dysbiosis
• Monogastric Animals
• Tight Junction Proteins

• 2020R1A2C1014007 National Research Foundation of Korea
• RS-2023-00245276 Ministry of Science and ICT

• B cell populations
• C57-CD40L-deficient mice
• IgA-production
• gut-associated secondary-lymphoid-organs
• unimmunised

• Mice
• Animals
• Inulin/pharmacology
• Gastrointestinal Microbiome
• Dextrans/pharmacology
• Mice, Inbred BALB C
• Dietary Supplements
• Prebiotics
• Weight Gain
• Lipid Metabolism Disorders
• Cholesterol/pharmacology

• Lymphofollicular hyperplasia
• Monkeypox (mpox)
• Outbreak
• PTGC
• Proctitis

• diffuse lymphoid tissue
• genital organ-associated lymphoid tissue
• goat
• lymphatic nodule
• mucosa-associated lymphoid tissue
• pig
• vaginal vestibule

• 19H03113 Japan Society for the Promotion of Science

The potential threat of global warming in the 21^st century is on the ecosystem through many aspects, including the negative impact of rising global temperature on the health of humans and animals, especially domestic animals. The damage caused by heat stress to animals has been more and more significant as the worldwide climate continues to rise, along with the breeding industry's expanding scale and stocking density, and it has become the most important stress-causing factor in southern China. In this review, we described the effects of heat stress on animal immune organs and immune system. The much-debated topic is how hyperthermia affects the tight junction barrier. Heat stress also induces inflammation in the body of animals causing low body weight and loss of appetite. This review also discussed that heat stress leads to hepatic disorder, and it also damages the intestine. The small intestine experiences ischemia, and the permeability of the intestine increases. Furthermore, the oxidative stress and mitogen-activated protein kinase (MAPK) pathways have a significant role in stress-induced cellular and organ injury. The study has shown that MAPK activity in the small intestine was increased by heat stress. Heat stress caused extreme small intestine damage, enhanced oxidative stress, and activated MAPK signaling pathways.

Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.

This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose).

In a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.

At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG.

Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile.

[https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].

• Nestlé Nutrition Institute

• Adenoviridae/genetics
• Adenovirus Infections, Human/epidemiology
• Adenoviruses, Human/genetics
• Cadherins/genetics
• Child
• Child, Preschool
• Gene Expression
• Humans
• Real-Time Polymerase Chain Reaction
• Receptors, Calcitriol/genetics

• microbiology
• endocrine system and metabolic diseases

• Dysbiosis/therapy
• Gastrointestinal Microbiome
• Homeostasis
• Humans
• Immunity
• Inflammation

Photobacterium damselae subsp. damselae is a pathogen that mainly infects a variety of fish species. There are many antibiotic-resistant strains of Photobacterium damselae subsp. damselae. In a previously published article, we described the production method for a novel oral biofilm vaccine. In the study reported herein, we confirmed the protective effect of the oral biofilm vaccine against Photobacterium damselae subsp. damselae. Twenty-eight days after vaccination, phagocytosis increased by 256% relative to the control group. The mean albumin–globulin ratios of the vaccine groups were significantly lower than the mean albumin–globulin ratios of the control group. There were no significant intergroup differences in lysozyme activity. Mean IgM titers were significantly higher in the vaccine group than in the control group. There was a significant upregulation of the TLR 3, IL-1β, and IL-8 genes in the spleen 28 days after vaccination. The cumulative mortality of the control fish was 84% after challenging fish with the Photobacterium damselae subsp. damselae, while the cumulative mortality of the oral biofilm vaccine (PBV) group was 32%, which was significantly higher than those of the whole-cell vaccine (PWV) and chitosan particle (CP) groups. There is minimal published research on the prevention and treatment of Photobacterium damselae subsp. damselae infection; therefore, this oral biofilm vaccine may represent a new method to fill this gap.

• bifidobacteria
• gut maturation
• gut microbiota
• infant formula
• intestinal immune response
• milk-derived oligosaccharides
• opportunistic pathogenic bacteria

Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the ‘gut–lung axis’ in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has triggered the global coronavirus disease 2019 (COVID-19) pandemic, in which respiratory symptoms of fever, cough and dyspnoea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhoea. Besides the gut–lung axis, it should be noted that the gut participates in numerous axes which may affect lung function, and consequently the severity of COVID-19, through several pathways. This article focuses on the latest evidence and the mechanisms that drive the operation of the gut–lung axis, and discusses the interaction between the gut–lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II, raising hypotheses and providing methods to guide future research on this new disease and its treatments.

• Coronavirus disease-19
• Dysbiosis
• Gut-lung axis
• Immunity
• Microbiota

Immunosenescence is a multi-faceted phenomenon at the root of age-associated immune dysfunction. It can lead to an array of pathological conditions, including but not limited to a decreased capability to surveil and clear senescent cells (SnCs) and cancerous cells, an increased autoimmune responses leading to tissue damage, a reduced ability to tackle pathogens, and a decreased competence to illicit a robust response to vaccination. Cellular senescence is a phenomenon by which oncogene-activated, stressed or damaged cells undergo a stable cell cycle arrest. Failure to efficiently clear SnCs results in their accumulation in an organism as it ages. SnCs actively secrete a myriad of molecules, collectively called senescence-associated secretory phenotype (SASP), which are factors that cause dysfunction in the neighboring tissue. Though both cellular senescence and immunosenescence have been studied extensively and implicated in various pathologies, their relationship has not been greatly explored. In the wake of an ongoing pandemic (COVID-19) that disproportionately affects the elderly, immunosenescence as a function of age has become a topic of great importance. The goal of this review is to explore the role of cellular senescence in age-associated lymphoid organ dysfunction and immunosenescence, and provide a framework to explore therapies to rejuvenate the aged immune system.

• cellular senescence
• immune senescence
• immunosenescence
• senescence associated secretory phenotype (SASP)
• thymus

Lactococcus garvieae (L. garvieae) is an important pathogen that causes enormous economic losses in both marine and freshwater aquaculture. At present, antibiotics are the only option for farmers to reduce the losses caused by L. garvieae. However, the usage of antibiotics leads to environmental pollution and the production of drug-resistant strains of bacteria. Therefore, vaccination is preferred as an alternative method to prevent infectious diseases. In this study, we describe an effective approach to the production of an oral biofilm vaccine, using bacteria grown on chitosan particles to form biofilms, and thus providing an inactive pathogen that enhances the immune response in fish. We observed the formation of a biofilm on chitosan particles and administered the novel oral biofilm vaccine to fish. We analyzed the immune responses, including antibody production, phagocytic ability, albumin/globulin ratio and immune-related genes, of vaccinated and control groups of black mullet. Our results show that the phagocytic ability of the biofilm vaccine group was 84%, which is significantly higher than that of the control group, and the antibody production in this group was significantly higher compared with the other group. The mRNA expression levels of immune-related genes (TLR2, IL-1β, TNF-α) were significantly upregulated in the spleen after vaccination. In challenge experiments, the relative percent survival (RPS) was 77% in the biofilm vaccine group, 18% in the whole-cell vaccine group, and 0% in the chitosan particle group at 32 days post-vaccination. In addition, we also found that the relative percent survival (RPS) at 1 day post-vaccination was 74% in the biofilm vaccine group, 42% in the whole-cell vaccine group, and 26% in the chitosan particle group. In both long-term and short-term challenge experiments, the viability of the biofilm vaccine group was significantly higher than that of the whole-cell, chitosan particle and PBS groups. We conclude that based on its protective effect, the L. garvieae biofilm vaccine is better than the whole-cell vaccine when challenged several weeks after vaccination. In addition, the biofilm vaccine also has a greater protective effect than the whole-cell vaccine when challenged immediately after vaccination. Therefore, the biofilm vaccine might represent a novel method for the prevention and treatment of L. garvieae infection.

• IgM
• Lactococcus garvieae
• Mugil cephalus
• oral biofilm vaccine

Pancreatic cancer is one of the most lethal cancers. It is a difficult cancer to treat, and the complexity surrounding the pancreatic tumour is one of the contributing factors. The microbiome is the collection of microorganisms within an environment and its genetic material. They reside on body surfaces and most abundantly within the human gut in symbiotic balance with their human host. Disturbance in the balance can lead to many diseases, including cancers. Significant advances have been made in cancer treatment since the introduction of immunotherapy, and the microbiome may play a part in the outcome and survival of patients with cancer, especially those treated with immunotherapy. Immunotherapy use in pancreatic cancer remains challenging. This review will focus on the potential interaction of the microbiome with pancreas cancer and how this could be manipulated.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.

• microbiome
• pancreatic ductal adenocarcinoma (PDAC)
• therapeutic manipulation

Emerging evidence accumulated over the past several years has uncovered intestinal CD4⁺ T cells as an essential mediator in modulating intestinal immunity in health and diseases. It has also been increasingly recognized that dietary and microbiota-derived factors play key roles in shaping the intestinal CD4⁺ T-cell compartment. This review aims to discuss the current understanding on how the intestinal T cell immune responses are disturbed by obesity and metabolic stress. In addition, we review how these changes influence systemic metabolic homeostasis and the T-cell-mediated crosstalk between gut and liver or brain in the progression of obesity and its related diseases. Lastly, we highlight the potential roles of some drugs that target intestinal T cells as a therapeutic treatment for metabolic diseases. A better understanding of the interaction among metabolites, bacterial signals, and T cell immune responses in the gut and their roles in systemic inflammation in metabolic tissues should shed new light on the development of effective treatment of obesity and related disorders.

• T cells
• dietary signals
• intestine
• microbiota
• obesity

• IBD
• biological therapy
• extraintestinal manifestation

• Microbial Metabolism
• Microbiome

• R01 DK125382 NIDDK NIH HHS
• R21 AT010366 NCCIH NIH HHS
• T32 GM128596 NIGMS NIH HHS
• P20 GM121344 NIGMS NIH HHS
• R25 HL088992 NHLBI NIH HHS

• Nutraceutical
• application
• cancer
• diabetes
• medicinal plants
• source

• Rabbit
• economic efficiency
• gene expression
• oligosaccharides
• prebiotics

• antibiotic resistance
• atopic diseases
• autoimmune diseases
• dysbiosis
• fetal microbiota
• gut microbiota
• infant microbiota
• necrotizing enterocolitis
• pregnancy
• preterm microbiota
• probiotic safety
• probiotics

• Dysbiosis/microbiology
• Dysbiosis/prevention & control
• Enterocolitis, Necrotizing/microbiology
• Enterocolitis, Necrotizing/prevention & control
• Female
• Gastrointestinal Microbiome
• Humans
• Infant
• Infant, Newborn
• Infant, Newborn, Diseases/microbiology
• Infant, Newborn, Diseases/prevention & control
• Male
• Perinatal Care/methods
• Probiotics/therapeutic use

Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.

• Cytokines
• immunity
• inulin
• morphology
• piglets
• polymerisation
• small intestine

Patients with gastrointestinal diseases frequently suffer from skeletal abnormality, characterized by reduced bone mineral density, increased fracture risk, and/or joint inflammation. This pathological process is characterized by altered immune cell activity and elevated inflammatory cytokines in the bone marrow microenvironment due to disrupted gut immune response. Gastrointestinal disease is recognized as an immune malfunction driven by multiple factors, including cytokines and signaling molecules. However, the mechanism by which intestinal inflammation magnified by gut-residing actors stimulates bone loss remains to be elucidated. In this article, we discuss the main risk factors potentially contributing to intestinal disease-associated bone loss, and summarize current animal models, illustrating gut-bone axis to bridge the gap between intestinal inflammation and skeletal disease.

• animal models
• bone loss
• gut inflammation
• mucosal immunity
• osteoclasts
• risk factors

• Antibiotic resistance
• Colorectal cancer
• Enterococcus
• Gene transfer
• Infection
• Probiotics
• Virulence

• Echinacea
• antioxidants
• fructans
• herbal medicine
• immunomodulation
• prebiotics

• Antioxidants/chemistry
• Antioxidants/isolation & purification
• Antioxidants/pharmacology
• Antiviral Agents/chemistry
• Antiviral Agents/isolation & purification
• Antiviral Agents/pharmacology
• Echinacea/chemistry
• Fructans/chemistry
• Fructans/isolation & purification
• Fructans/pharmacology
• Immune System/drug effects
• Immune System/immunology
• Immunomodulation
• Plant Extracts/chemistry
• Plant Extracts/isolation & purification
• Plant Extracts/pharmacology
• Viruses/drug effects
• Viruses/immunology