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Postbiotics Unveiled: The Next Emerging Trend in Functional Foods.
The global population is expected to reach 9.7 billion by 2050, with demand for food increasing by up to 56%. Postbiotics are a safe and reliable substitute for probiotics, which are described as preparations of non-viable bacteria and/or their metabolic byproducts. Data for this narrative review was collected using Goggle scholar and PubMed from 2006 to 2026. Major bioactive compounds such as short-chain fatty acids, peptides, polysaccharides, vitamins, and cell fragments contribute to immunomodulatory, antioxidant, metabolic, and gut-brain axis effects. Preclinical and clinical research shows that they can improve insulin sensitivity, control cytokine signaling, strengthen epithelial barrier integrity, and protect against obesity, type 2 diabetes mellitus, and depression. Postbiotics have also been found to improve mineral absorption and folate synthesis, and possess anti-sarcopenic actions. Several commercial products are available because of their health benefits. Thus, postbiotics are a revolutionary development in microbiome-based treatments; however, to completely understand their therapeutic potential, it is necessary to standardize, achieve mechanistic clarity, and ensure regulatory alignment.
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Mental health in early pregnancy: Interplay of objectively measured lifestyles, gut microbiota, and metabolomics.
Prenatal anxiety symptoms (AS) and depression symptoms (DS) in early pregnancy substantially impact maternal-infant health, but their pathophysiological mechanisms remain unclear. We conducted a multimodal assessment of 161 early-pregnant women. DS exhibited significantly longer standing/sitting durations and shorter nocturnal sleep and nap times (p < 0.05). AS was associated with lower fiber intake (p = 0.018). AS and DS had more complex microbial co-occurrence networks with more extensive metabolomic changes. DS was characterized by dysregulated cysteine/methionine metabolism and Bifidobacterium-mediated modulation of standing/sleep effects. Machine learning achieved best DS discrimination by combining physical activity, diet, and microbiome data (AUC = 0.877), while metabolomics alone best discriminated AS (AUC = 0.844). In conclusion, AS is associated with metabolomic dysregulation and fiber deficiency, while DS is associated with sedentary behavior and microbiota-metabolite disruption. This study establishes a precision framework prioritizing fiber interventions for AS and activity/sleep modulation targeting microbiota-metabolite pathways for DS.
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Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.
AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy. MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index ≥ 35 kg/m2 and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n = 15) or autologous FMT (their own stool; n = 13) delivered in the caecum and were followed for 3 months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores. RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P < 0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P < 0.05) but not in the autologous group. CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.
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Serum Cyclic Pentapeptide Cyclo(D-Trp-D-Asp-Pro-D-Val-Leu) as a Candidate Diagnostic Biomarker for Depression-Anxiety Comorbidity.
INTRODUCTION: The comorbidity rate of depression and anxiety disorders is as high as 50%, with patients suffering from both conditions facing an elevated risk of suicide. Given the challenges in clinical diagnosis, there is an urgent need for objective diagnostic biomarkers to accurately identify patients with comorbid depression and anxiety disorders. METHODS: The case-control study enrolled 77 participants, including healthy controls (n = 38) and patients with comorbid depression and anxiety disorders (n = 39). Serum levels of short peptides were assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Binary logistic regression and receiver operating characteristic analysis (ROC) were employed to identify potential biomarkers, while decision curve analysis (DCA) was performed to evaluate the clinical utility of the candidate cyclic pentapeptide. RESULTS: A total of 25 differentially expressed short peptides were identified, among which 19 were significantly downregulated, and 6 were upregulated. Logistic regression analysis revealed that reduced levels of cyclo (D-trp-D-asp-pro-D-val-leu) were associated with an increased risk of comorbid depression and anxiety disorders. The area under the ROC curve (AUC) for this cyclic pen-tapeptide in diagnosing comorbid depression and anxiety disorders was 0.941 (95% CI, 0.884-0.997; P < 0.0001). DCA demonstrated that the cyclic pentapeptide provides meaningful net benefits when the threshold probability exceeded 0.11. Notably, this cyclic pentapeptide is an endothelin A receptor antagonist, which is implicated in vasoconstriction, hypertension, and anxiety, and elevated blood pressure was indeed observed in the patient cohort. DISCUSSION: The identified cyclic pentapeptide serves as a potential diagnostic tool, linking the pathophysiology of comorbid depression and anxiety disorders to the endothelin system. This association offers a novel integrative perspective on the co-occurring psychiatric and cardiovascular manifestations observed in these patients. CONCLUSION: In conclusion, this study identifies a specific cyclic pentapeptide as a promising serum biomarker that may facilitate the objective diagnosis of patients with comorbid depression and anxiety disorders. Its biological role as an endothelin A receptor antagonist not only provides a potential tool for clinical differentiation but also suggests a novel pathophysiological link to cardiovascular comorbidities, thereby offering new directions for elucidating the underlying mechanisms of these conditions.
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Gut Microbial β-Glucuronidase Inhibition via Catalytic Cycle Interception.
Microbial β-glucuronidases (GUSs) cause severe gut toxicities that limit the efficacy of cancer drugs and other therapeutics. Selective inhibitors of bacterial GUS have been shown to alleviate these side effects. Using structural and chemical biology, mass spectrometry, and cell-based assays, we establish that piperazine-containing GUS inhibitors intercept the glycosyl-enzyme catalytic intermediate of these retaining glycosyl hydrolases. We demonstrate that piperazine-based compounds are substrate-dependent GUS inhibitors that bind to the GUS-GlcA catalytic intermediate as a piperazine-linked glucuronide (GlcA, glucuronic acid). We confirm the GUS-dependent formation of inhibitor-glucuronide conjugates by LC-MS and show that methylated piperazine analogs display significantly reduced potencies. We further demonstrate that a range of approved piperazine- and piperidine-containing drugs from many classes, including those for the treatment of depression, infection, and cancer, function by the same mechanism, and we confirm through gene editing that these compounds selectively inhibit GUS in living bacterial cells. Together, these data reveal a unique mechanism of GUS inhibition and show that a range of therapeutics may impact GUS activities in the human gut.
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Dysregulation of Oral Microbial Eicosapentaenoic Acid Induced by Chronic Restraint Stress Exacerbates Periodontitis via M1 Macrophage Polarization.
The intricate interplay between chronic psychological stress and periodontitis, mediated by oral microbiota and macrophage polarization, remains largely enigmatic. Here, we demonstrate that chronic restraint stress (CRS) exacerbates periodontitis by inducing oral microbial dysbiosis and a consequential shift in host metabolism. Clinical observations reveal a significant correlation between depressive symptoms and the severity of periodontitis, which is underpinned by a distinct oral microbiome. Crucially, fecal microbiota transplantation from CRS-exposed mice into germ-free mice was sufficient to transmit the heightened periodontitis phenotype, establishing a causal role for the stress-altered microbiota. Metabolomic profiling identified a depletion of eicosapentaenoic acid (EPA) in stressed, ligature-induced periodontitis mice. Mechanistically, supplementation with EPA ameliorates periodontitis by suppressing the NF-κB signaling pathway, thereby inhibiting the pro-inflammatory M1 polarization of macrophages. Our findings unveil a novel gut-oral axis mediated by microbiota and metabolites under stress, and position the omega-3 fatty acid EPA as a promising therapeutic agent for mitigating stress-aggravated inflammatory disorders.
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Mechanical allodynia corresponds to Oprm1 downregulation within the descending pain network of male and female rats exposed to neonatal immune challenge.
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation. In the present study male and female Sprague-Dawley rats were administered either the inflammatory endotoxin lipopolysaccharide (LPS; 0.05mg/kg, i.p.) or saline (equivolume) on postnatal days (PND) 3 and 5. During adolescence, hind paw mechanical withdrawal thresholds were evaluated using an electronic von Frey anesthesiometer. Animals challenged neonatally with LPS (nLPS) had increased pain sensitivity on this measure which was associated with decreased Oprm1 expression in the prefrontal cortex (PFC) and periaqueductal gray (PAG) of both male and female rats. Although a 'second hit' with LPS in adolescence (aLPS) did not confer protection or reveal additional vulnerabilities, aLPS given to animals treated neonatally with saline was associated with increased pain sensitivity, but only in females. Interestingly, adolescent inflammatory challenge decreased Hcrt2 mRNA in the PAG and elevated Trpv1 in the PAG and PFC of both sexes. There was no effect of inflammatory treatment on either anxiety or depressive-like behavior suggesting that affective functioning did not account for differences in mechanical pain sensitivity. Finally, a preliminary investigation demonstrated that administration of a broad spectrum antibiotic cocktail attenuated the mechanical sensitivity that followed nLPS. Together, these data extend upon evidence that inflammation imparts long term changes in quality of life and pain responses via interference within the descending pain network. Moreover, they highlight a potential window of opportunity to target the microbiota-gut-brain axis and reverse pain processing disturbances following perinatal inflammation.
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Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review.
BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. METHODS: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. RESULTS: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17-50%), IBS-D (37-62%) and IBS-C (4-25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). CONCLUSIONS: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.
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Activity Engagement Across Stages of Cognitive Health.
Objective: This study aims to examine activity engagement across stages of cognitive health among older adults. Methods: We used a cross-sectional study analysis of baseline data collected as part of the prospective Microbiome in Aging of Gut and Brain (MiaGB) longitudinal study; the study period was August 2022 to December 2023. Health history and activity engagement questionnaires and the Montreal Cognitive Assessment (MoCA) were used to examine the study objective. One-way ANOVA and chi-squared tests, with Bonferroni post hoc analyses, assessed group differences. Results: The weighted samples reflected 417 participants: 54% females, 70.7% White, with an average age of 72 (±8.7) years, 90% with at least high school education, and 75% self-reported medium income status. Results suggested that individuals who scored ≤17 points on the MoCA had an average age of 84 years, were White, non-Hispanic, female, had less than a high school education, and medium income status (p < 0.001). Significant differences were found in active engagement in all health behaviors (p < 0.05). The frequency of engagement in activities was all statistically significant (p < 0.05), except the frequency of looking after grandchildren (p > 0.05). Older adults who scored ≤17 MoCA points reported higher rates of hypertension, osteoarthritis, and depression compared with individuals who scored higher on the MoCA assessment. Conclusions: Older adults with lower cognitive status report a higher rate of clinical ailments and have less engagement in meaningful activities. We should promote meaningful activities to improve the quality of life in older adults with decreased cognition. We make recommendations for appropriate modifications for activity engagement across cognitive health levels.
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Microbiome and ileum transcriptome revealed the boosting effects of selenium yeast on egg production in aged laying hens.
The declines in laying performance during the late production period have adverse effects on the length of the production cycle. Improving the nutrition of laying hens is a crucial measure to reverse this declination. This study investigated the effect of selenium yeast (SY) on egg production, ileal gene expression and microbiota, as well as elucidating their associations in aged laying hens. A total of 375 Jinghong laying hens at 76 weeks old were randomly assigned into 5 dietary treatments, which included a selenium-deficient basal diet based on corn-soybean meal, and dietary supplementation of SY at 0.15, 0.30 and 0.45 mg/kg, and sodium selenite at 0.45 mg/kg. The results showed that SY ameliorated the depression in aged laying performance in the 0.30 mg/kg group (P < 0.01). Selenium yeast significantly increased ileum selenium concentration (P < 0.05), and SY groups had higher selenium deposition efficiency than the sodium selenite group. Functional enrichment and Short Time-series Expression Miner (STEM) analysis indicated that SY activated metabolic progress (e.g., glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism), immune response and oxidative stress response. Four hub genes including thioredoxin reductase 1 (TXNRD1), dihydrolipoamide dehydrogenase (DLD), integrin linked kinase (ILK) and leucine zipper tumor suppressor 2 (LZTS2) were involved in intestinal metabolism which was closely associated with selenium deposition/status. Moreover, the relative abundance of Veillonella, Turicibacter and Lactobacillus was significantly increased, but the relative abundance of Stenotrophomonas was significantly decreased by SY supplementation. Multi-omics data integration and Canonical correspondence analysis (CCA) showed that both the ileum selenium content and the laying rate were highly correlated with pathways and bacteria enriched in metabolism and immune response. Meanwhile, the "switched on" gene prostate stem cell antigen (PSCA) had a positive relationship with Veillonella and a negative relationship with the opportunistic pathogens Stenotrophomonas. Overall, our study offered insight for the further exploration of the role of SY on boosting egg production and balancing ileum intestinal flora in aged laying hens.