COL1A1 as a potential new biomarker and therapeutic target for type 2 diabetes.

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC-MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

Lactic acid bacteria alleviate liver damage caused by perfluorooctanoic acid exposure via antioxidant capacity, biosorption capacity and gut microbiota regulation.

Perfluorooctanoic acid (PFOA) is an environmental pollutant that has multiple toxic effects. Although some medicines and functional food ingredients are currently being used to alleviate the biological toxicity effects caused by PFOA, these candidates all show potential side effects and cannot prevent the accumulation of PFOA in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of PFOA. However, new research has shown that lactic acid bacteria (LAB) can alleviate toxicity caused by exposure to foreign substances. In this study, multiple strains of LAB with different adsorption capacities or antioxidant capacities were used to analyse their mitigation effects of on liver damage caused by PFOA exposure. The results showed that the adsorption capacity and antioxidant capacity of LAB could alleviate the liver toxicity of PFOA to a certain extent. Moreover, treatment with some strains of LAB was able to recover the gut microbiota dysbiosis caused by PFOA exposure, such as by increasing the relative abundances of Patescibacteria, Proteobacteria, Akkermansia and Alistipes or decreasing the abundances of Bacteroides and Blautia. In addition, a strain with neither outstanding antioxidant capacity nor adsorption capacity also reversed the decline in short-chain fatty acid levels caused by PFOA exposure. The ability of these strains to relieve gut microbiota dysbiosis partly explains the inconsistency between the capacity for antioxidant or PFOA adsorption and the ability of the strains to alleviate PFOA toxicity. The results indicate that the PFOA adsorption capacity and antioxidant capacity of LAB may be involved in the alleviation of PFOA liver toxicity. In addition, LAB could also alleviate liver damage caused by PFOA by adjusting the gut microbiota and short-chain fatty acid content. Therefore, some strains of LAB can be used as a potentially safe dietary supplement to relieve PFOA-induced liver damage.

Role of Green Macroalgae Enteromorpha Prolifera Polyphenols in the Modulation of Gene Expression and Intestinal Microflora Profiles in Type 2 Diabetic Mice.

Effects of green macroalgae 55% ethanolic extract Enteromorpha prolifera through an ultrafiltration membrane of 3 kDa (EPE3k) on antidiabetic activity, gut microbiota, and regulation mechanism were investigated in high-fat/high-sucrose diet and streptozocin-induced diabetic mice. The structural characterizations of its major compounds in EPE3k were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Furthermore, the intestinal microflora modulation in diabetic mice was also investigated with high-throughput 16S rRNA gene sequencing. The proposed presence of polyphenols in EPE3k was confirmed. EPE3k could significantly decrease the fasting blood glucose and improve fasting glucose tolerance. The hypoglycemic effect of EPE3k was via activation of phosphatidylinositol 3-kinase and suppression of c-Jun N-terminal kinase in liver. EPE3k treatment significantly increased the relative abundance of Akkermansia and decreased the proportion of Alistipes and Turicibacter. The above results indicated that EPE3k could be provided as a new potential therapy for the treatment of type 2 diabetic mellitus.

Dietary nucleotides drive changes in infant fecal microbiota in vitro and gut microbiota-gut-brain development in neonatal rats: A potential "nitrogen source" for early microbiota growth.

Various dietary factors in human milk are important nutrients for the formation of the infant gut microbiota (GM). While promoting the growth of the GM, some human milk components that are difficult to absorb and utilize will be broken down by the GM, and converted into nutrients that the baby can use, such as breast milk oligosaccharides-the 'carbon source' for infant GM. This study reveals that nucleotides (NTs), significant non-protein nitrogen sources in human milk, can enhance the abundance of beneficial microbial genera such as g_Bifidobacterium, g_Bacteroides, and g_Blautia in in vitro fecal fermentation fluids of infants at low doses (2 mg/mL). Conversely, high doses of NTs (20 mg/mL) increased the abundance of g_Escherichia-Shigella. Furthermore, low-dose NTs fermentation broth significantly enhanced the expression of neurodevelopmental marker genes such as Tuj1, Sox2, Dcx, and NeuN in NE-4C neural stem cells, whereas a single NTs digestion broth did not exhibit significant activity. However, in vivo studies using neonatal rats as a model demonstrated that both low-dose NTs fermentation broth and NTs digestive juices promoted behavioral development in neonatal rats (PND 20) and neuron maturation in the prefrontal cortex and hippocampus. Non-targeted metabolomics results indicate that low-dose dietary NTs promote the production of certain neuroregulatory metabolites in infant fecal fermentation, such as uridine, L-tyrosine, L-glutamic acid, and succinic acid. These findings suggest that NTs may serve as an important "nitrogen source" during GM formation in early life and have a dose effect in driving the development of the microbiota-gut-brain axis in early life.

Bifidobacteria with indole-3-lactic acid-producing capacity exhibit psychobiotic potential via reducing neuroinflammation.

The escalating global prevalence of depression demands effective therapeutic strategies, with psychobiotics emerging as a promising solution. However, the molecular mechanisms governing the neurobehavioral impact of psychobiotics remain elusive. This study reveals a significant reduction in hippocampal indole-3-lactic acid (ILA) levels in depressed mice, which is ameliorated by the psychobiotic Bifidobacterium breve. In both human subjects and mice, the ILA increase in the circulatory system results from bifidobacteria supplementation. Further investigation identifies the key aromatic lactate dehydrogenase (Aldh) gene and pathway in bifidobacteria responsible for ILA production. Importantly, the antidepressant effects are nullified in the Aldh mutants compared to the wild-type strain. At the bifidobacteria species level, those with Aldh exhibit heightened antidepressant effects. Finally, this study emphasizes the antidepressant efficacy of psychobiotic-derived ILA, potentially mediated by aryl hydrocarbon receptor (AhR) signaling activation to alleviate neuroinflammation. This study unveils the molecular and genetic foundations of psychobiotics' antidepressant effects, offering insights for microbial therapies targeting mood disorders.

Dynamics of the Gut Microbiota and Faecal and Serum Metabolomes during Pregnancy-A Longitudinal Study.

Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, Bifidobacterium communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the Lachnospiraceae FCS020 group and Ruminococcaceae UCG-003. Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with Ruminococcus1 and Ruminococcaceae UCG-013 making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota-metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.

Detection of colonization capacity of probiotic Bifidobacterium breve CCFM1025 in the human gut.

Aim: To detect the gut colonization capacity of Bifidobacterium breve CCFM1025 with clinical antidepressant-like effects. Materials & methods: A unique gene sequence of B. breve CCFM1025 was discovered based on the genome analysis of 104 B. breve strains and a strain-specific primer (1025T5) was designed. In vitro and in vivo samples were used to validate the specificity and quantitative capability of this primer in the PCR system. Results: Quantitative PCR using strain-specific primers enabled absolute quantification of CCFM1025 in fecal samples within 104-1010 cells/g (R2 >0.99). CCFM1025 remained highly detectable in volunteer feces 14 days after cessation of administration, demonstrating its favorable colonization characteristics. Conclusion: CCFM1025 can colonize the healthy human gut.

Bifidobacterium adolescentis Is Effective in Relieving Type 2 Diabetes and May Be Related to Its Dominant Core Genome and Gut Microbiota Modulation Capacity.

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant Bifidobacterium species (B. bifidum and B. adolescentis, which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more B. adolescentis strains appeared to be superior in alleviating T2D symptoms than B. bifidum strains. This effect was closely related to the ability of B. adolescentis to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with B. bifidum, B. adolescentis had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, glgP. This may be one of the reasons why B. adolescentis is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.

The Comparative Analysis of Genomic Diversity and Genes Involved in Carbohydrate Metabolism of Eighty-Eight Bifidobacterium pseudocatenulatum Isolates from Different Niches of China.

Eighty-eight Bifidobacterium pseudocatenulatum strains, which were isolated from human, chicken and cow fecal samples from different niches of China, were compared genomically in this study to evaluate their diversity. It was found that B. pseudocatenulatum displayed a closed pan-genome, including abundant glycoside hydrolase families of the carbohydrate active enzyme (CAZy). A total of 30 kinds of glycoside hydrolases (GHs), 14 kinds of glycosyl transferases (GTs), 13 kinds of carbohydrate-binding modules (CBMs), 6 kinds of carbohydrate-esterases (CEs), and 2 kinds of auxiliary activities (AAs) gene families were identified across the genomes of the 88 B. pseudocatenulatum strains. Specifically, this showed that significant differences were also present in the number of 10 carbohydrate-active enzyme gene families (GT51, GH13_32, GH26, GH42, GH121, GH3, AA3, CBM46, CE2, and CE6) among the strains derived from the hosts of different age groups, particularly between strains from infants and those from other human age groups. Twelve different individuals of B. pseudocatenulatum from four main clusters were selected for further study to reveal the genetic diversity of carbohydrate metabolism-related genes within the same phylogenetics. The animal experiment showed that 3 weeks of oral administration and 1 week after cessation of administration of these strains did not markedly alter the serum routine inflammatory indicators in mice. Furthermore, the administration of these strains did not significantly cause adverse changes in the gut microbiota, as indicated by the α- and ß-diversity indexes, relative to the control group (normal diet). Beyond that, FAHBZ9L5 significantly increased the abundance of B. pseudocatenulatum after 3 weeks and significantly increased the abundance of acetic acid and butyric acid in the host's intestinal tract 3 and 4 weeks after the first administration, respectively, compared with the control group. Corresponding to this, comparative genomic analyses of 12 B. pseudocatenulatum suggest that FAHBZ9L5-specific genes were rich in ABC transporters and carbohydrate esterase. Combining the results of comparative genomics analyses and animal experiment, it is suggested that the strains containing certain gene clusters contribute to another competitive growth advantage of B. pseudocatenulatum, which facilitates its intestinal carbohydrate metabolism in a host.

Structural characterization and antioxidant effect of green alga Enteromorpha prolifera polysaccharide in Caenorhabditis elegans via modulation of microRNAs.

A water-soluble heteropolysaccharide was isolated and purified from Enteromorpha prolifera by DEAE-52 and Bio-Gel P-2 column chromatography. Fourier transform infrared spectroscopy (FTIR), high performance liquid chromatography (HPLC), multi-angle laser light scattering (MALLS), and nuclear magnetic resonance (NMR) spectroscopy were used to characterize the structure of E. prolifera polysaccharide degradation (EPP-1). Its anti-oxidative activity was determined in Caenorhabditis elegans via modulation of microRNAs. The average molecular weight of EPP-1 was 4.28 kDa. It contained six types of linkage units as →2)-ß-d-GlcpA-(1→, →3,6)-ß-d-Manp-(1→, →4)-α-d-Glcp-(1→, →6)-ß-d-Galp-(1→, ß-l-Rhap-(1→, and →4)-ß-d-GalpA-(1→. The mean lifespan, ultraviolet-induced oxidative stress, and thermotolerance in C. elegans were improved after treatment of EPP-1. Moreover, EPP-1 significantly increased the total superoxide dismutase levels and decreased the malondialdehyde levels in C. elegans. Intracellular reactive oxygen species accumulation and DNA damage were ameliorated by up-regulation of SKN-1 and DAF-16 expression through miR-48 and miR-51 miR-186 down-regulation. In vivo studies demonstrated that EPP-1 might be applied in functional foods as the antioxidative and anti-ageing ingredient.

Antidiabetic Potential of Green Seaweed Enteromorpha prolifera Flavonoids Regulating Insulin Signaling Pathway and Gut Microbiota in Type 2 Diabetic Mice.

This study aimed to investigate the antidiabetic activity of water-ethanol extract of green macroalgae Enteromorpha prolifera (EPW) and its flavonoid-rich fraction less than 3 kDa (EPW3) in type 2 diabetic mice induced by streptozotocin and a high-sucrose/high-fat diet. The major active compounds were identified using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-tandem mass spectrometry. Quantitative gene expression analysis of the insulin signaling pathway was performed. The effects of EPW3 on gut microflora in diabetic mice were analyzed by high-throughput 16S rRNA gene sequencing. The results showed EPW3 treatment decreased the fasting blood glucose, improved oral glucose tolerance, and protected against liver and kidney injury with reduced inflammation in diabetic mice. The active principle of EPW3 revealed hypoglycemic effect as indicated by activation of the IRS1/PI3K/AKT and inhibition of the JNK1/2 insulin pathway in liver. Furthermore, the treatment significantly enriched the abundance of Lachnospiraceae and Alisties, which were positive correlation of metabolic phenotypes. These findings indicated that EPW3 possessed great therapeutic potential as adjuvant therapy for type 2 diabetes.

Anti-ageing and antioxidant effects of sulfate oligosaccharides from green algae Ulva lactuca and Enteromorpha prolifera in SAMP8 mice.

Oligosaccharides from green algae Ulva lactuca (ULO) and Enteromorpha prolifera (EPO) were used for investigation of anti-ageing effects and the underlying mechanism in SAMP8 mice. The structural properties of ULO and EPO were analyzed by fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and agarose gel electrophoresis. These oligosaccharides enhanced the glutathione, superoxide dismutase, catalase, and telomerase levels and total antioxidant capicity, and decreased the levels of malondialdehyde and advanced glycation end products. After ULO and EPO treatment, the levels of inflammatory factors, including IFN-γ, TNF-α, and IL-6, decreased; the BDNF and ChAT levels increased; and hippocampal neurons were protected. Downregulation of the p53 and FOXO1 genes and upregulation of the Sirt1 gene indicated that ULO and EPO have potential therapeutic effects in the prevention of ageing in SAMP8 mice. By 16S rRNA gene high-throughput sequencing, the abundance of Desulfovibrio was discovered to be markedly different in mice treated with ULO and EPO. The abundances of Verrucomicrobiaceae, Odoribacteraceae, Mogibacteriaceae, Planococcaceae, and Coriobacteriaceae were positively correlated with age-related indicators. These results demonstrated that oligosaccharides from U. lactuca and E. prolifera are ideal candidate compounds that can be used in functional foods and pharmaceuticals to prevent ageing.