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Cell Metabolism May 2024The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including...
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.
Topics: Animals; Gastrointestinal Microbiome; Mice; Depression; Male; Mice, Inbred C57BL; Humans; Homovanillic Acid; Synapses; Hippocampus; Neurons; Female
PubMed: 38582087
DOI: 10.1016/j.cmet.2024.03.010 -
Cell Host & Microbe Jan 2024Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient...
Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.
Topics: Humans; Mice; Animals; Bifidobacterium longum; Carcinoma, Hepatocellular; Prospective Studies; Recovery of Function; Retrospective Studies; Liver Neoplasms; Probiotics
PubMed: 38091982
DOI: 10.1016/j.chom.2023.11.011 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2023The beneficial effects of probiotic consumption on age-related decline in cerebral function have been previously reported in the literature; however, the mechanistic... (Randomized Controlled Trial)
Randomized Controlled Trial
Gut microbiota indole-3-propionic acid mediates neuroprotective effect of probiotic consumption in healthy elderly: A randomized, double-blind, placebo-controlled, multicenter trial and in vitro study.
BACKGROUND & AIMS
The beneficial effects of probiotic consumption on age-related decline in cerebral function have been previously reported in the literature; however, the mechanistic link between gut and brain interactions has not yet been fully elucidated. Therefore, this study aimed to identify the role of gut microbiota-derived metabolites in gut-brain interactions via blood metabolomic profiling analysis in clinical trials and in vitro mechanistic studies.
METHODS
A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted in 63 healthy elderly individuals (≥65 years of age). Participants were administered either placebo (placebo group, N = 31) or probiotic capsules (Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI; probiotics group, N = 32) for 12 weeks. Global and targeted metabolomic profiling analyses of their blood samples were then performed using H nuclear magnetic resonance and liquid chromatography-mass spectrometry methods, both at baseline and at the end of the trial. Gut microbial analysis was conducted using the 16S ribosomal ribonucleic acid gene sequencing method. Subsequently, microglial BV2 cells were treated in vitro with indole-3-propionic acid (IPA) following lipopolysaccharide stimulation, and neuronal SH-SY5Y cells were treated with conditioned media from the BV2 cells. Finally, the levels of pro-inflammatory cytokines in BV2 cells and neurotrophins in SH-SY5Y cells were quantified using a real-time polymerase chain reaction or enzyme-linked immunosorbent assay.
RESULTS
The metabolomic profiling analyses showed that probiotic consumption significantly altered the levels of metabolites involved in tryptophan metabolism (P < 0.01). Among these metabolites, gut microbiota-produced IPA had a 1.91-fold increase in the probiotics group (P < 0.05) and showed a significant relation to gut bacterial profiles (P < 0.01). Elevated IPA levels were also positively associated with the level of serum brain-derived neurotropic factor (BDNF) in the probiotics group (r = 0.28, P < 0.05), showing an inverse trend compared to the placebo group. In addition, in vitro treatment with IPA (5 μM) significantly reduced the concentration of proinflammatory TNF-α in activated microglia (P < 0.05), and neuronal cells cultured with conditioned media from IPA-treated microglia showed a significant increase in BDNF and nerve growth factor production (P < 0.05).
CONCLUSIONS
These results show that gut microbiota-produced IPA plays a role in protecting the microglia from inflammation, thus promoting neuronal function. Therefore, this suggests that IPA is a significant mediator linking the interaction between the gut and the brain in the elderly with probiotic supplementation.
Topics: Humans; Aged; Gastrointestinal Microbiome; Neuroprotective Agents; Brain-Derived Neurotrophic Factor; Culture Media, Conditioned; Neuroblastoma; Probiotics; Double-Blind Method
PubMed: 37150125
DOI: 10.1016/j.clnu.2023.04.001 -
Frontiers in Nutrition 2023While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported,...
While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of and genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9-12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of and species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With species, we observed significant associations with motor functions, while showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of = 0.012) and in interaction with LNFP-I (value of = 0.007). Additionally, 3-FL showed a positive association with gross motor ( = 0.027) and visual reception ( = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for species and LNT [ ( = 0.011) and ( = 0.022)], and positive associations for expressive language with 3'-SL and ( = 0.01), 6'-SL and ( = 0.019), and LNFP-I and ( = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and and species reveal different candidate pathways through which HMOs, and species potentially interact to impact cognitive development in infancy.
PubMed: 37457984
DOI: 10.3389/fnut.2023.1216327 -
Free Radical Biology & Medicine Jul 2023Acetaminophen (APAP) overdose is the most common driver of drug-induced liver injury (DILI) worldwide, and the gut microbiome plays a crucial role in this process. In...
Acetaminophen (APAP) overdose is the most common driver of drug-induced liver injury (DILI) worldwide, and the gut microbiome plays a crucial role in this process. In this study, we estimated the effect of Bifidobacterium longum R0175 on APAP-induced liver injury in mice and discovered that B. longum R0175 alleviated liver injury by diminishing inflammation, reducing oxidative stress levels, inhibiting hepatocyte death and improving APAP-induced microbiome dysbiosis. Further studies revealed that the antioxidative effects of B. longum R0175 were primarily due to activation of the Nrf2 pathway, which was supported by the Nrf2 pathway inhibitor ML385 counteracting these ameliorative effects. B. longum R0175 modified intestinal metabolites, especially the key metabolite sedanolide, which could activate the Nrf2 pathway and contribute to the protective effects against APAP-induced liver injury. Moreover, we found that sedanolide exhibited close interrelationships with specific microbial taxa, indicating that this factor may be derived from gut microbes. In conclusion, our work demonstrated that B. longum R0175 could reduce oxidative damage, inflammation and hepatocyte death by activating the Nrf2 pathway. Importantly, we identified the microbiota-derived metabolite sedanolide, which was first discovered in the mouse intestine, as a key agonist of the Nrf2 pathway and primary effector of B. longum R0175 in APAP challenge. These findings provide new perspectives for APAP overdose therapy and demonstrate the enormous potential of B. longum R0175 in alleviating acute liver injury.
Topics: Mice; Animals; Acetaminophen; NF-E2-Related Factor 2; Chemical and Drug Induced Liver Injury, Chronic; Bifidobacterium longum; Liver; Oxidative Stress; Chemical and Drug Induced Liver Injury; Inflammation; Mice, Inbred C57BL
PubMed: 37003500
DOI: 10.1016/j.freeradbiomed.2023.03.026 -
Frontiers in Microbiology 2024Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota... (Review)
Review
Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including and , and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.
PubMed: 38357350
DOI: 10.3389/fmicb.2024.1292004 -
Nutrients Jul 2023Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with (1 × 10 CFU/daily) on... (Randomized Controlled Trial)
Randomized Controlled Trial
Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with (1 × 10 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.
Topics: Humans; Adult; Hydrocortisone; Bifidobacterium; Probiotics; Bifidobacterium longum; Stress, Psychological; Double-Blind Method
PubMed: 37513541
DOI: 10.3390/nu15143122 -
Nutrients Jul 2023Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and clinical studies clearly indicate... (Review)
Review
Wound healing is a multi-factorial response to tissue injury, aiming to restore tissue continuity. Numerous recent experimental and clinical studies clearly indicate that probiotics are applied topically to promote the wound-healing process. However, the precise mechanism by which they contribute to healing is not yet clear. Each strain appears to exert a distinctive, even multi-factorial action on different phases of the healing process. Given that a multi-probiotic formula exerts better results than a single strain, the pharmaceutical industry has embarked on a race for the production of a formulation containing a combination of probiotics capable of playing a role in all the phases of the healing process. Hence, the object of this review is to describe what is known to date of the distinctive mechanisms of each of the most studied probiotic strains in order to further facilitate research toward the development of combinations of strains and doses, covering the whole spectrum of healing. Eleven probiotic species have been analyzed, the only criterion of inclusion being a minimum of two published research articles.
Topics: Bifidobacterium; Probiotics; Wound Healing
PubMed: 37447381
DOI: 10.3390/nu15133055 -
Foods (Basel, Switzerland) Dec 2023Strategies to stabilize and support overall infant health by increasing the number of in the infant gut are of interest, but few studies have systematically addressed... (Review)
Review
BACKGROUND
Strategies to stabilize and support overall infant health by increasing the number of in the infant gut are of interest, but few studies have systematically addressed this issue. We aimed to evaluate the efficacy and safety of use in infants using meta-analysis.
METHODS
We searched PubMed, EMBASE, Cochrane Library of Systematic Reviews, and SinoMed for publications until 27 July 2022. The main outcomes of interest were weight gain, risk of necrotizing enterocolitis (NEC), and adverse events. Two authors independently performed study screening, risk of bias assessment, and data extraction. Outcome data were extracted from each included study and combined using mean difference (MD) or risk ratio (RR) and finally combined using a fixed-effect model or random-effect model.
RESULTS
A total of 4481 relevant studies were identified, of which 15 were found to be eligible for randomized controlled trials and were included in the meta-analysis. The combined extracted data showed that the intervention group containing had a significantly lower risk of NEC (RR = 0.539, 95% CI: 0.333, 0.874) compared to the control group. There was no statistical difference between the intervention and control groups regarding weight gain (MD = 0.029, 95% CI: -0.032, 0.090), the occurrence of adverse events (RR = 0.986, 95% CI: 0.843, 1.153), and serious adverse events (RR = 0.881, 95% CI: 0.493, 1.573).
CONCLUSIONS
may significantly reduce the risk of NEC in infants as well as being safe; thus, further research evidence is needed on whether there is a benefit on weight gain.
PubMed: 38137255
DOI: 10.3390/foods12244451 -
Nutrients Aug 2023The fermentation and quality characteristics of yogurt were investigated according to the inoculation concentration of . The total sugar content of yogurt decreased as...
The fermentation and quality characteristics of yogurt were investigated according to the inoculation concentration of . The total sugar content of yogurt decreased as the fermentation time increased, and with an increased concentration of treatment the fermentation time decreased rapidly. As fermentation progressed, the lactose content decreased rapidly at the beginning and gradually decreased as the pH decreased. Depending on the treatment concentration, the lactose content varied from 0.29 ± 0.01 to 0.47 ± 0.01% and was 0.5% or less in all experimental groups. The experimental group inoculated with 0.0015% of displayed the best results in all categories, including pH, total acidity, lactic acid content, solid non-fat content, and total lactic acid bacteria count, which are factors that determine the quality of yogurt. In summary, the experimental group inoculated with 0.0015% of was determined to be the highest quality yogurt.
PubMed: 37571428
DOI: 10.3390/nu15153490