An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD).

Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.

In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures from HBV-Associated Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains, Levilactobacillus brevis SR52-2 (L. brevis SR52-2) and LeviLactobacillus delbrueckii subsp. bulgaicus Q80 (L. delbrueckii Q80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p < 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated with L. brevis SR52-2 and L. delbrueckii Q80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specifically L. brevis SR52-2 and L. delbrueckii Q80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.

Lactiplantibacillus plantarum 124 Modulates Sleep Deprivation-Associated Markers of Intestinal Barrier Dysfunction in Mice in Conjunction with the Regulation of Gut Microbiota.

Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.

Gut microbiota: Candidates for a novel strategy for ameliorating sleep disorders.

The aim of this review was to evaluate the feasibility of treating sleep disorders using novel gut microbiota intervention strategies. Multiple factors can cause sleep disorders, including an imbalance in the gut microbiota. Studies of the microbiome-gut-brain axis have revealed bidirectional communication between the central nervous system and gut microbes, providing a more comprehensive understanding of mood and behavioral regulatory patterns. Changes in the gut microbiota and its metabolites can stimulate the endocrine, nervous, and immune systems, which regulate the release of neurotransmitters and alter the activity of the central nervous system, ultimately leading to sleep disorders. Here, we review the main factors affecting sleep, discuss possible pathways and molecular mechanisms of the interaction between sleep and the gut microbiota, and compare common gut microbiota intervention strategies aimed at improving sleep physiology.

Metabolism of resistant starch RS3 administered in combination with Lactiplantibacillus plantarum strain 84-3 by human gut microbiota in simulated fermentation experiments in vitro and in a rat model.

This study aimed to investigate the metabolic and population responses of gut microbiota to resistant starch (RS3) in the presence of exogenous Lactiplantibacillus plantarum strain 84-3 (Lp84-3) in vitro and in vivo. Lp84-3 promoted acetate, propionate, and butyrate production from RS3 by gut microbiota and increased Lactobacillus and Blautia contents in vitro. Furthermore, in the presence of Lp84-3, starch granules presented a "dot-by-hole" fermentation pattern. Administration of Lp84-3 with RS3 increased the level of SCFA-producing Faecalibaculum, Parabacteroides, Alistipes, and Anaeroplasma in the faeces of rates, with Lactobacillus and Akkermansia representing the key genera that significantly promoted SCFAs, especially propionate and butyrate. Lp84-3 with RS3 promoted genes related to tryptophan synthase (EC 4.2.1.20) and beta-glucosidase (EC 3.2.1.21) in faecal bacteria. Our findings highlight the ability of Lp84-3 to enhance RS3 degradation, possibly by promoting SCFA-producing bacteria, and indicate that Lp84-3 could be a potential probiotic with a beneficial effect on gut microbiota.

Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus.

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world's longevity town-Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity.

Bifidobacterium longum 070103 Fermented Milk Improve Glucose and Lipid Metabolism Disorders by Regulating Gut Microbiota in Mice.

BACKGROUND: Fermented milk is beneficial for metabolic disorders, while the underlying mechanisms of action remain unclear. This study explored the benefits and underlying mechanisms of Bifidobacterium longum 070103 fermented milk (BLFM) in thirteen-week high-fat and high-sugar (HFHS) fed mice using omics techniques. METHODS AND RESULTS: BLFM with activated glucokinase (GK) was screened by a double-enzyme coupling method. After supplementing BLFM with 10 mL/kg BW per day, fasting blood glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and leptin were significantly reduced compared with the HFHS group. Among them, the final body weight (BW), epididymal fat, perirenal fat, and brown fat in BLFM group had better change trends than Lacticaseibacillus rhamnosus GG fermented milk (LGGFM) group. The amplicon and metabolomic data analysis identified Bifibacterium as a key gut microbiota at regulating glycolipid metabolism. BLFM reverses HFHS-induced reduction in bifidobacteria abundance. Further studies showed that BLFM significantly reduces the content of 3-indoxyl sulofphate associated with intestinal barrier damage. In addition, mice treated with BLFM improved BW, glucose tolerance, insulin resistance, and hepatic steatosis. CONCLUSION: BLFM consumption attenuates obesity and related symptoms in HFHS-fed mice probably via the modulation of gut microbes and metabolites.

Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension.

Pseudomonas protegens FJKB0103 Isolated from Rhizosphere Exhibits Anti-Methicillin-Resistant Staphylococcus aureus Activity.

Staphylococcus aureus is amongst the most virulent pathogens, causing chronic and life-threatening human infections. Methicillin-resistant S. aureus (MRSA) are multidrug-resistant strains, and the ability of forming a biofilm reduces their sensitivity to antibiotics. Thus, the alternative compounds inhibiting both resistant strains and biofilm formation are in high demand. In our study, the strain FJKB0103 was isolated from the rhizosphere of Garcinia mangostana, showing strong anti-MRSA activity. We performed molecular phylogenic analysis, analyzed average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH), and biochemical characteristics to identify strain FJKB0103 as Pseudomonas protegens. Herein, the genome of strain FJKB0103 was sequenced and subjected to antiSMASH platform, mutational, and functional analyses. The FJKB0103 draft genome was 6,776,967 bp with a 63.4% G + C content, and 16 potential secondary compound biosynthetic clusters in P. protegens FJKB0103 were predicted. The deletion mutant and complementary analysis suggested that DAPG was the anti-MRSA compound. Further tests showed that MRSA strains were sensitive to DAPG, and the lysis of bacterial cells was observed at a high concentration of DAPG. Additionally, DAPG inhibited the biofilm formation of MRSA at subinhibitory concentration. These results suggested that DAPG might be a good alternative treatment to control infections caused by MRSA.

Metagenomics-Based Analysis of the Age-Related Cumulative Effect of Antibiotic Resistance Genes in Gut Microbiota.

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world's longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.

Evaluation of the Cholesterol-Lowering Mechanism of Enterococcus faecium Strain 132 and Lactobacillus paracasei Strain 201 in Hypercholesterolemia Rats.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillusparacasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.

Selective Isolation of Bifidobacterium From Human Faeces Using Pangenomics, Metagenomics, and Enzymology.

Bifidobacterium, an important genus for human health, is difficult to isolate. We applied metagenomics, pangenomics, and enzymology to determine the dominant glycoside hydrolase (GH) families of Bifidobacterium and designed selective medium for Bifidobacterium isolation. Pangenomics results showed that the GH13, GH3, GH42, and GH43 families were highly conserved in Bifidobacterium. Metagenomic analysis of GH families in human faecal samples was performed. The results indicated that Bifidobacterium contains core GHs for utilizing raffinose, D-trehalose anhydrous, D(+)-cellobiose, melibiose, lactulose, lactose, D(+)-sucrose, resistant starch, pullulan, xylan, and glucan. These carbohydrates as the main carbon sources were applied for selective media, which were more conducive to the growth of bifidobacteria. In the medium with lactose, raffinose and xylan as the main carbon sources, the ratio of cultivable bifidobacteria to cultivable microorganisms were 89.39% ± 2.50%, 71.45% ± 0.99%, and 53.95% ± 1.22%, respectively, whereas the ratio in the ordinary Gifu anaerobic medium was only 17.90% ± 0.58%. Furthermore, the species significantly (p < 0.05) varied among samples from different individuals. Results suggested that xylan might be a prebiotic that benefits host health, and it is feasible to screen and isolate bifidobacteria using the oligosaccharides corresponding to the specific GHs of bifidobacteria as the carbon sources of the selective media.

Integrated Multi-Omics for Novel Aging Biomarkers and Antiaging Targets.

Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism is unclear. Advancements in high-throughput technology provide new opportunities for omics research to understand the pathological process of various complex human diseases. However, single-omics technologies only provide limited insights into the biological mechanisms of diseases. DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles and perform certain biological functions together. In this review, we summarize multi-omics methods based on the most relevant biomarkers in single-omics to better understand molecular functions and disease causes. The integration of multi-omics technologies can systematically reveal the interactions among aging molecules from a multidimensional perspective. Our review provides new insights regarding the discovery of aging biomarkers, mechanism of aging, and identification of novel antiaging targets. Overall, data from genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, and systems biology contribute to the identification of new candidate biomarkers for aging and novel targets for antiaging interventions.

Probiotics supplementation improves hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes mellitus: An update of meta-analysis.

Background: Although many studies have shown that consumption of probiotics is relevant to diabetes, the effects of probiotics improves clinical outcomes in type 2 diabetes have yielded conflicting results. The aim of this meta-analysis was conducted to assess the effects of probiotics supplementation on glycemic, blood lipids, pressure and inflammatory control in type 2 diabetes.Methods: PubMed, Web of science, Embase and the Cochrane Library databases were searched for relevant studies from February 2015 up to Janurary 2020, with no language restrictions. The pooled results were calculated with the use of a random-effects model to assess the impact of supplemental probiotics on glycemic, blood lipids, pressure and inflammatory control in type 2 diabetes. Additionally, subgroup analysis was conducted based on patients age, body mass index (BMI), country and duration of the probiotics supplement, respectively.Results: 13 studies were included in this meta-analysis, involving a total of 818 participants in 8 countries. Overall, compared with control groups, the subjects who received multiple species of probiotics had a statistically significant reduction in fasting blood sugar (FBS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) and tumor necrosis factor (TNF) -α [standardized mean difference (SMD): -0.89 mg/Dl, 95% CI: -1.66, -0.12 mg/dL; SMD: -0.43, 95% CI: -0.63, -0.23; SMD: -0.19 mg/dL, 95% CI: -0.36, -0.01 mg/dL; SMD: -0.23 mg/dL, 95% CI: -0.40, -0.05 mg/dL; SMD: -5.61 mmHg, 95% CI: -9.78, -1.45 mmHg; SMD: -3.41 mmHg, 95% CI: -6.12, -0.69 mmHg; and SMD: 6.92 pg/ml, 95% CI: 5.95, 7.89 pg/ml, respectively]. However, the subjects who received single-species of probiotic or probiotic with co-supplements in food only changed FBS, HOMA-IR, DBP and TG levels. Moreover, subgroup analyses revealed that the effects of probiotics supplementation on FBS, HMOA-IR, SBP and DBP are significantly influenced by patients age, body mass index (BMI), country and duration of the probiotics supplement.Conclusion: Our analysis revealed that glycemic, lipids, blood pressure and inflammation indicators are significantly improved by probiotic supplementation, particularly the subjects who ages ≤ 55, baseline BMI< 30 kg/m2, duration of intervention more than 8 weeks, and received multiple species probiotic.