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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 -
Journal of Clinical and Translational... Aug 2023Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship...
BACKGROUND AND AIMS
Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether and could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota.
METHODS
Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice.
RESULTS
Both strains were able to attenuate mass gain (<0.001), insulin resistance (<0.001), and liver lipid deposition (<0.001). They also reduced the levels of the pro-inflammatory factors (<0.05) and the proportion of Th17 (<0.001), while elevating the proportion of Treg (<0.01). Both strains activated hepatic FXR while suppressing intestinal FXR (<0.05), and elevating tight junction protein expression (<0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function.
CONCLUSIONS
Administration of or alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.
PubMed: 37408808
DOI: 10.14218/JCTH.2022.00415 -
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 -
Endocrinologia, Diabetes Y Nutricion Jan 2024Irritable bowel syndrome (IBS) is a gastrointestinal functional disorder mainly characterised by abdominal pain, bloating and altered bowel habits. Dysbiosis might seem... (Review)
Review
Irritable bowel syndrome (IBS) is a gastrointestinal functional disorder mainly characterised by abdominal pain, bloating and altered bowel habits. Dysbiosis might seem to be involved in the pathogenesis of the disease. Probiotics represent a potential treatment, since these could favour the functional microbiota and improve symptoms. The aim was to review the effectiveness of the use of probiotics in IBS symptomatology, analysing the influence of duration and dose. 18 articles were included. At the individual level, Lactobacillus, Bifidobacterium and Bacillus could be useful in the treatment of symptoms. Bifidobacterium bifidum reported the best results (1 × 10 CFU/day for 4 weeks). The most effective combination was 2 Lactobacillus strains, one of Bifidobacterium and one of Streptococcus (4 × 10 CFU/day for 4 weeks). Future clinical trials should confirm these results and analyse the difference between individual and combined treatments.
Topics: Humans; Irritable Bowel Syndrome; Probiotics; Lactobacillus; Bifidobacterium; Abdominal Pain
PubMed: 38331656
DOI: 10.1016/j.endien.2024.01.003 -
Microorganisms Oct 2023Childhood obesity is a major public health problem worldwide with an increasing prevalence, associated not only with metabolic syndrome, insulin resistance,... (Review)
Review
Childhood obesity is a major public health problem worldwide with an increasing prevalence, associated not only with metabolic syndrome, insulin resistance, hypertension, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), but also with psychosocial problems. Gut microbiota is a new factor in childhood obesity, which can modulate the blood lipopolysaccharide levels, the satiety, and fat distribution, and can ensure additional calories to the host. The aim of this review was to assess the differences and the impact of the gut microbial composition on several obesity-related complications such as metabolic syndrome, NAFLD, or insulin resistance. Early dysbiosis was proven to be associated with an increased predisposition to obesity. Depending on the predominant species, the gut microbiota might have either a positive or negative impact on the development of obesity. Prebiotics, probiotics, and synbiotics were suggested to have a positive effect on improving the gut microbiota and reducing cardio-metabolic risk factors. The results of clinical trials regarding probiotic, prebiotic, and synbiotic administration in children with metabolic syndrome, NAFLD, and insulin resistance are controversial. Some of them (, , and ) were proven to reduce the body mass index in obese children, and also improve the blood lipid content; others (, , , , , and fructo-oligosaccharides) failed in proving any effect on lipid parameters and glucose metabolism. Further studies are necessary for understanding the mechanism of the gut microbiota in childhood obesity and for developing low-cost effective strategies for its management.
PubMed: 38004665
DOI: 10.3390/microorganisms11112651 -
Signal Transduction and Targeted Therapy Sep 2023The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool...
The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.
Topics: Humans; COVID-19 Vaccines; Gastrointestinal Microbiome; BNT162 Vaccine; Cohort Studies; COVID-19; SARS-CoV-2; Antibodies, Neutralizing
PubMed: 37743379
DOI: 10.1038/s41392-023-01629-8 -
Immunity & Ageing : I & A Oct 2023Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and...
Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways.
Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice. Oral administration of Lp, Bb, or their mix (LB) increased grip strength and treadmill running distance and time. They significantly increased muscle weight in aged mice. They also increased AKT activation, PGC1α, SIRT1, and myosin heavy chain (MyHC) expression, MyHC-positive cell population, and cell size in the gastrocnemius (GA) muscle, while FOXO3a and NF-κB activation, MuRF1, muscle atrophy F-box, and p16 expression, and NF-κBCD11c cell population decreased. Furthermore, they reduced cognitive impairment-like behavior, IL-6 expression, FOXO3a activation, and NF-κB-positive cell population in the hippocampus, GA, and colon, while hippocampal brain-derived neurotropic factor expression increased. They shifted gut microbiota composition in aged mice: they increased Akkermansiaceae and Bacteroidaceae populations, which were positively correlated with total muscle weight and MyHC expression, and decreased Odoribacteraceae and Deferribacteriaceae populations, which were positively correlated with MuRF1 and IL-6 expression. LB alleviated sarcopenia- and cognitive impairment-like symptoms more potently than Lp or Bb alone. Based on these findings, probiotics, particularly Lp, Bb, and LB, can alleviate aging-dependent sarcopenia and cognitive impairment by regulating gut microbiota-mediated AKT, NF-κB, and/or FOXO3a signaling pathways.
PubMed: 37872562
DOI: 10.1186/s12979-023-00381-5 -
Genome Analysis of E3, Structural Characteristics, and Antioxidant Properties of Exopolysaccharides.Foods (Basel, Switzerland) Aug 2023In this study, the antioxidant properties of intact cells (IC), cell-free supernatant (CFS), and cell-free extracts (CFE) and whole genome sequencing of E3 ( E3), as...
In this study, the antioxidant properties of intact cells (IC), cell-free supernatant (CFS), and cell-free extracts (CFE) and whole genome sequencing of E3 ( E3), as well as the structural characteristics and antioxidant properties of EPS-1, EPS-2, and EPS-3, were evaluated. The results revealed that intact cells (IC), cell-free supernatant (CFS), and cell-free extracts (CFE) had potent DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), hydroxyl, and superoxide anion radical scavenging capacities, among which CFS was the best. At the genetic level, we identified a strong carbohydrate metabolism capacity, an EPS synthesis gene cluster, and five sugar nucleotides in E3. Therefore, we extracted cEPS from E3 and purified it to obtain EPS-1, EPS-2, and EPS-3. EPS-1, EPS-2, and EPS-3 were heteropolysaccharides with an average molecular weight of 4.15 × 10 Da, 3.67 × 10 Da, and 5.89 × 10 Da, respectively. The EPS-1 and EPS-2 are mainly comprised of mannose and glucose, and the EPS-3 is mainly comprised of rhamnose, mannose, and glucose. The typical characteristic absorption peaks of polysaccharides were shown in Fourier transform infrared spectroscopy (FT-IR spectroscopy). The microstructural study showed a rough surface structure for EPS-1, EPS-2, and EPS-3. Furthermore, EPS-1, EPS-2, and EPS-3 exhibited potent DPPH, hydroxyl, and superoxide anion radical scavenging capacities. Correlation analysis identified that antioxidant capacities may be influenced by various factors, especially molecular weight, chemical compositions, and monosaccharide compositions. In summary, the EPS that was produced by E3 may provide insights into health-promoting benefits in humans.
PubMed: 37627987
DOI: 10.3390/foods12162988 -
Frontiers in Nutrition 2023Substantial attention has been paid to the various effects of metformin on liver diseases; the liver is the targeted organ where metformin exerts its antihyperglycemic... (Review)
Review
Substantial attention has been paid to the various effects of metformin on liver diseases; the liver is the targeted organ where metformin exerts its antihyperglycemic properties. In non-alcoholic fatty liver disease (NAFLD), studies have shown that metformin affects the ATP/AMP ratio to activate AMPK, subsequently governing lipid metabolism. The latest research showed that low-dose metformin targets the lysosomal AMPK pathway to decrease hepatic triglyceride levels through the PEN2-ATP6AP1 axis in an AMP-independent manner. Metformin regulates caspase-3, eukaryotic initiation factor-2a (eIF2a), and insulin receptor substrate-1 (IRS-1) in palmitate-exposed HepG2 cells, alleviating endoplasmic reticulum (ER) stress. Recent observations highlighted the critical association with intestinal flora, as confirmed by the finding that metformin decreased the relative abundance of while increasing and . The suppression of intestinal farnesoid X receptor (FXR) and the elevation of short-chain fatty acids resulted in the upregulation of tight junction protein and the alleviation of hepatic inflammation induced by lipopolysaccharide (LPS). Additionally, metformin delayed the progression of cirrhosis by regulating the activation and proliferation of hepatic stellate cells (HSCs) via the TGF-β1/Smad3 and succinate-GPR91 pathways. In hepatocellular carcinoma (HCC), metformin impeded the cell cycle and enhanced the curative effect of antitumor medications. Moreover, metformin protects against chemical-induced and drug-induced liver injury (DILI) against hepatotoxic drugs. These findings suggest that metformin may have pharmacological efficacy against liver diseases.
PubMed: 38192642
DOI: 10.3389/fnut.2023.1327814 -
Nature Communications Jul 2023Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully... (Meta-Analysis)
Meta-Analysis
Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.
Topics: Male; Humans; Female; Gastrointestinal Microbiome; Bifidobacterium; Microbiota; Bacteria
PubMed: 37452041
DOI: 10.1038/s41467-023-39931-2