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Dietary supplementation with vitamin C ameliorates the adverse effects of Salmonella Enteritidis-challenge in broilers by shaping intestinal microbiota.
Salmonella Enteritidis (SE) infection is not only a leading cause of poor production performance and compromised animal welfare in broilers but also a potential threat to public health. Two experiments were conducted to evaluate the effects of dietary supplemental vitamin C (VC) on SE challenged-broilers. In experiment 1, one hundred eighty 1-day-old Arbor Acre broilers were randomly allocated into 3 treatments, with 0, 500, or 1,000 mg/kg VC included in the diet. In experiment 2, dietary VC at 0 or 500 mg/kg, with or without SE challenge was applied in a 2 × 2 factorial arrangement in 6 randomized complete blocks. In experiment 1, addition with 500 mg/kg VC increased BW and infectious bursal disease (IBD) titer of broilers on 35 D (P < 0.05), whereas 1,000 mg/kg VC had no effects on the IBD titer (P > 0.05) compared with the control group. In experiment 2, SE challenge depressed BW on 11 and 21 D (P < 0.05 and P = 0.088, respectively), whereas increased mortality and hepatic bacterial translocation (P < 0.05) on 21 D. Further, SE challenge resulted in lower villus height in jejunum, lower microbial richness, and diversity, whereas higher abundance of Enterobacteriaceae in cecum (P < 0.05). Importantly, supplementation with VC increased BW on both 21 and 35 D (P < 0.05 and P = 0.088, respectively) and enhanced the intestinal health by improving villus morphology and microbial structure as indicated by higher cecal microbial richness and Firmicutes to Bacteroidetes ratio, while lower abundance of Enterobacteriaceae (P < 0.05). In addition, birds fed with 500 mg/kg VC in the diet had significantly increased jejunal secretory immunoglobulin A levels, T lymphocytes stimulation index, and serum total antioxidant capability compared with groups without VC (P < 0.05). In conclusion, SE challenge induced lower production performance and higher mortality in broilers. However, dietary supplementation with VC ameliorated SE-caused damage in broilers by improving the intestinal health, partly mediated by shaping the structure of cecal microbiota.
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Regulation of Intestinal Permeability in Health and Disease: Possible Therapeutic Applications.
Intestinal permeability is the process by which certain substances pass through the intestinal barrier and enter the bloodstream to reach the tissues and organs where they are needed. This vital process is regulated by various physiological mechanisms, depending on the type of molecule being translocated, from ions and water molecules to large peptides and vitamins. However, under certain conditions, intestinal permeability can increase, exposing the body to the passage of unwanted molecules and pathogenic microorganisms. The various mechanisms involved in increased intestinal permeability include the zonulin pathway, intestinal epithelial cell death, intestinal dysbiosis, and transcytosis. Each of these mechanisms is activated by certain stimuli, and may occur in isolation or together. The translocation of molecules and pathogens has been linked to the development or worsening of certain pathologies, such as acute pancreatitis, sepsis, inflammatory bowel diseases, irritable bowel syndrome, celiac disease, systemic lupus erythematosus, obesity, depression, and schizophrenia. This is mainly due to the inflammatory response generated in response to the translocated microorganisms. Research has been conducted to develop therapies to decrease intestinal permeability in several diseases. This review summarizes knowledge related to pathways that regulate intestinal permeability, diseases associated with increased intestinal permeability, and advances in potential treatments.
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Revealing the magic of acupuncture based on biological mechanisms: A literature review.
Acupuncture has been used to treat various disease for more than 3,000 years in China and other Asian countries. As a complementary and alternative therapy, it has gained increasing popularity and acceptance among public and healthcare professionals in the West. Over the past few decades, basic and clinical research on acupuncture has made considerable progress. Internationally recognized evidence from clinical studies has been published, a preliminary system to clinically evaluate acupuncture has been created, and some clinical guidelines have been formulated. Moreover, scientists have strived to explore the physiological and biological mechanisms of acupuncture. Some basic studies have indicated that acupuncture has various actions, such as analgesic, muscle relaxing, anti-inflammatory, mild anxiolytic, and antidepressant actions, with possible biological mechanisms such as central sensitization, neurotransmitters, the intestinal flora, immune regulation, oxidative stress, and neuroinflammation. The current review describes the common indications for acupuncture recommended by the WHO and the use of acupuncture in China, the United States, Australia, and several other countries. This review then summarized the mechanisms by which acupuncture treats common conditions including lower back pain (LBP), ischemic stroke, depression, and irritable bowel syndrome (IBS) and it also cited specific acupuncture points for treating these conditions. The hope is that this review will provide useful information for both acupuncturists and researchers to better understand the mechanisms of acupuncture and reasons for its usage.
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Efficacy and Mechanism of Synbiotics in Relieving Functional Constipation: Optimized by Generation Time.
Background: Functional constipation (FC) represents a highly prevalent gastrointestinal disorder, affecting approximately 8.5% of the population in China. It is frequently associated with anxiety and depression, significantly impairing patients' quality of life. Conventional microecological therapeutic approaches predominantly rely on empirical probiotic-prebiotic combinations. However, these pairings are seldom selected based on strain-specific metabolic characteristics, ultimately leading to suboptimal therapeutic synergy. Methods: The generation time (GT) of four constipation-relief strains was measured across eight oligosaccharides to identify optimal substrates for synbiotic formulation. The GT-optimized synbiotic was verified in a loperamide-induced mouse model vs. single probiotics/prebiotics. The related mechanisms of were assessed through 16S rDNA sequencing, targeted metabolomics, and qPCR. Results: The GT-optimized synbiotic significantly outperformed all single components. Specifically, the synbiotic significantly decreased the time to first black stool and increased fecal water content. Mechanistically, it restored colonic neurotransmitter balance, suppressed aquaporin expression, enriched butyrate-producing bacteria, and repaired barrier integrity. Overall, these effects work together, increasing the moisture content of the feces and accelerating intestinal peristalsis, ultimately alleviating constipation. Conclusions: We propose a GT-guided precision-pairing strategy that identifies optimal prebiotics based on strain-specific generation times, demonstrating synergistic enhancement of short-chain fatty acid (SCFA) production, enteric neurotransmitter signaling, and aquaporin-mediated water transport. This GT guided synbiotic approach shows promise in preclinical models and warrants validation in human trials.
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A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome.
Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-mapTM dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.
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Differences in the human gut microbiota with varying depressive symptom severity scores.
Depression is a prevalent mental health disorder, and its incidence has increased further because of the coronavirus disease 2019 (COVID-19) pandemic. The gut microbiome has been suggested as a potential target for mental health treatment because of the bidirectional communication system between the brain and gastrointestinal tract, known as the gut-brain axis. We aimed to investigate the relationship between the human gut microbiome and depression screening by analyzing the abundance and types of microbiomes among individuals living in Japan, where mental health awareness and support may differ from those in other countries owing to cultural factors. We used a data-driven approach to evaluate the gut microbiome of participants who underwent commercial gut microbiota testing services and completed a questionnaire survey that included a test for scoring depressive tendencies. Our data analysis results indicated that no significant differences in gut microbiome composition were found among the groups based on their depression screening scores. However, the results also indicated the potential existence of a few differentially abundant bacterial taxa. Specifically, the detected bacterial changes in abundance suggest that the Bifidobacteriaceae, Streptococcaceae, and Veillonellaceae families are candidates for differentially abundant bacteria. Our findings should contribute to the growing body of research on the relationship between gut microbiome and mental health, highlighting the potential of microbiome-based interventions for depression treatment. The limitations of this study include the lack of clear medical information on the participants' diagnoses. Future research could benefit from a larger sample size and more detailed clinical information.
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Systematic review of bidirectional interaction between gut microbiome, miRNAs, and human pathologies.
MicroRNAs (miRNAs) and the gut microbiome are key regulators of human health, with emerging evidence highlighting their complex, bidirectional interactions in chronic diseases. miRNAs, influence gene expression and can modulate the composition and function of the gut microbiome, impacting metabolic and immune processes. Conversely, the microbiome can affect host miRNA expression, influencing inflammatory pathways and disease susceptibility. This systematic review examines recent studies (2020-2024) focusing exclusively on human subjects, selected through rigorous inclusion and exclusion criteria. Studies were included if they investigated the interaction between miRNAs and the gut microbiome in the context of gastrointestinal diseases, obesity, autoimmune diseases, cognitive and neurodegenerative disorders, and autism. In vitro, in vivo and in silico analyses were excluded to ensure a strong translational focus on human pathophysiology. Notably, miRNAs, stable and abundant in patients, are emerging as promising biomarkers of microbiome-driven inflammation. This systematic review provides an overview of miRNAs, their regulatory effects on bacterial strains, and their associations with specific diseases. It also explores therapeutic advances and the potential of miRNA-based therapies to restore microbial balance and reduce inflammation.
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Review: Enhancing gastrointestinal health in dairy cows.
Due to their high energy requirements, high-yielding dairy cows receive high-grain diets. This commonly jeopardises their gastrointestinal health by causing subacute ruminal acidosis (SARA) and hindgut acidosis. These disorders can disrupt nutrient utilisations, impair the functionalities of gastrointestinal microbiota, and reduce the absorptive and barrier capacities of gastrointestinal epithelia. They can also trigger inflammatory responses. The symptoms of SARA are not only due to a depressed rumen pH. Hence, the diagnosis of this disorder based solely on reticulo-rumen pH values is inaccurate. An accurate diagnosis requires a combination of clinical examinations of cows, including blood, milk, urine and faeces parameters, as well as analyses of herd management and feed quality, including the dietary contents of NDF, starch and physical effective NDF. Grain-induced SARA increases acidity and shifts availabilities of substrates for microorganisms in the reticulo-rumen and hindgut and can result in a dysbiotic microbiota that are characterised by low richness, diversity and functionality. Also, amylolytic microorganisms become more dominant at the expense of proteolytic and fibrolytic ones. Opportunistic microorganisms can take advantage of newly available niches, which, combined with reduced functionalities of epithelia, can contribute to an overall reduction in nutrient utilisation and increasing endotoxins and pathogens in digesta and faeces. The reduced barrier function of epithelia increases translocation of these endotoxins and other immunogenic compounds out of the digestive tract, which may be the cause of inflammations. This needs to be confirmed by determining the toxicity of these compounds. Cows differ in their susceptibility to poor gastrointestinal health, due to variations in genetics, feeding history, diet adaptation, gastrointestinal microbiota, metabolic adaptation, stress and infections. These differences may also offer opportunities for the management of gastrointestinal health. Strategies to prevent SARA include balancing the diet for physical effective fibre, non-fibre carbohydrates and starch, managing the different fractions of non-fibre carbohydrates, and consideration of the type and processing of grain and forage digestibility. Gastrointestinal health disorders due to high grain feeding may be attenuated by a variety of feed supplements and additives, including buffers, antibiotics, probiotics/direct fed microbials and yeast products. However, the efficacy of strategies to prevent these disorders must be improved. This requires a better understanding of the mechanisms through which these strategies affect the functionality of gastrointestinal microbiota and epithelia, and the immunity, inflammation and 'gastrointestinal-health robustness' of cows. More representative models to induce SARA are also needed.
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Rationale, design, and statistical analysis plan for a randomized, double-blind, placebo-controlled trial of Limosilactobacillus reuteri to support mother-infant bonding and maternal socioemotional functioning in postpartum women at increased risk for postpartum depression.
BACKGROUND: Postpartum depression (PPD) is common and can impair early mother-infant bonding. Oxytocin (OXT) supports socioemotional adaptation, yet intranasal OXT yields supraphysiological exposure and mixed results. The probiotic Limosilactobacillus reuteri (L. reuteri) increases endogenous oxytocin levels in rodents, suggesting that it may enhance OXT signaling via gut-brain pathways in humans. We designed a proof-of-concept trial to test whether postpartum L. reuteri improves early mother-infant bonding and maternal mental health, impulse control, and emotion recognition. METHODS: In this randomized, double-blind, placebo-controlled trial, mothers aged ≥18 years at elevated PPD risk (history of depression, prior PPD, and/or increased prenatal depressive symptoms) received 6 weeks of once-daily L. reuteri or placebo, stratified by delivery mode (vaginal/Cesarean section). The primary endpoint is mother-infant bonding quality at Week 6; secondary endpoints include maternal mental health, impulse control, and emotion recognition at Week 6. Salivary OXT at Week 2 serves as a mechanistic endpoint. RESULTS: Forty-six participants (mean age ± SD: 34.3 ± 4.5 years) were enrolled and randomized; 38 (82.6%) completed the Week-6 visit. Baseline characteristics are reported. CONCLUSION: This trial evaluates whether a lactation-compatible L. reuteri intervention targeting endogenous OXT improves early mother-infant bonding and maternal well-being. Findings will inform feasibility, safety, and effect size estimates, clarify OXT's mechanistic role in PPD pathophysiology, and guide development of microbiome-based therapeutics for perinatal mental health. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04472065.
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Fasting the brain for mental health.
Unfavorable socioeconomic and geopolitical conditions such as poverty, violence and inequality increase vulnerability to mental disorders. Also, exposure to a poor nutrition such as high-energy dense (HED) diets has been linked to alterations in brain function, leading to anxiety, addiction, and depression. HED diets rich in saturated fatty acids or obesity can activate the innate immune system in the brain, especially microglia, increasing proinflammatory cytokines such as interleukin 1 beta (IL1-β) and interleukin 6 (IL-6), in part, by the stimulation of toll-like receptor 4 (TLR4) and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Intermittent fasting (IF), an eating protocol characterized by alternating periods of fasting with periods of eating, has gained recognition as a weight-management strategy to reduce obesity. Accordingly, during IF inflammation and brain function can be modulated by production of ketone bodies and modulation of the intestinal microbiota, which also promote the induction of brain-derived neurotrophic factor (BDNF), which is involved in neurogenesis and neuronal plasticity. Although IF has contributed to reduce body weight and improve metabolic profiles, its influence on mental health remains an evolving field of research. Here, we provide experimental evidence supporting the role of IF reducing neuroinflammation as a valuable approach to improve mental health.