-
Molecular Medicine Reports Aug 2024Chronic low‑grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin...
Chronic low‑grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin (LF) has a biological function in regulating intestinal flora. The present study aimed to investigate the therapeutic and anti‑-inflammatory effects of LF in obese mice based on intestinal flora. A total of 30 C57BL/6 mice were divided into three groups consisting of 10 mice each. Subsequently, one group was fed a normal diet (Group K), another group was fed a high‑fat diet (Group M) and the remaining group switched from regular drinking to drinking 2% LF water (Group Z2) after 2 weeks of high‑fat diet; all mice were fed for 12 weeks. After the experiment, the mouse blood lipid and lipopolysaccharide levels, levels of inflammatory factors and intestinal tight junction proteins were assessed. Mouse stool samples were analyzed using 16S ribosomal RNA sequencing. The results showed that LF reduced serum total cholesterol, triglycerides and low‑density lipoprotein levels, elevated high‑density lipoprotein levels, suppressed metabolic endotoxemia and attenuated chronic low‑grade inflammatory responses in obese mice. In addition, LF upregulated zonula occludens‑1 and occludin protein expression levels in the intestine, thereby improving intestinal barrier integrity. LF altered the intestinal microbial structure of obese mice, reduced the ratio of and an elevated ratio of , modifying the bacterial population to the increased relative abundance of and .
Topics: Animals; Lactoferrin; Gastrointestinal Microbiome; Mice; Obesity; Male; Inflammation; Mice, Inbred C57BL; Diet, High-Fat; Mice, Obese; Occludin; Lipopolysaccharides
PubMed: 38873986
DOI: 10.3892/mmr.2024.13262 -
The Journal of Nutritional Biochemistry Jun 2024Glucose metabolic disorders, prevalent in numerous metabolic diseases, have become a pressing global public health concern. Artemisinin (ART) and its derivatives,...
Glucose metabolic disorders, prevalent in numerous metabolic diseases, have become a pressing global public health concern. Artemisinin (ART) and its derivatives, including artesunate (ARTs) and artemether (ARTe), have shown potential as metabolic regulators. However, the specific effects of ART and its derivatives on glucose metabolism under varying nutritional conditions and the associated molecular mechanisms remain largely unexplored. In this study, we examined the impact of ART, ARTs, and ARTe on glucose homeostasis using a mouse model subjected to different dietary regimens. Our findings revealed that ART, ARTs, and ARTe increased blood glucose levels in mice on a normal-chow diet (ND) while mitigating glucose imbalances in high-fat diet (HFD) mice. Notably, treatment with ART, ARTs, and ARTe had contrasting effects on in vivo insulin signaling, impairing it in ND mice and enhancing it in HFD mice. Moreover, the composition of gut microbiota underwent significant alterations following administration of ART and its derivatives. In ND mice, these treatments reduced the populations of bacteria beneficial for improving glucose homeostasis, including Parasutterella, Alloprevotella, Bifidobacterium, Ileibacterium, and Alistipes. In HFD mice, there was an increase in the abundance of beneficial bacteria (Alistipes, Akkermanisia) and a decrease in bacteria known to negatively impact glucose metabolism (Coprobacillus, Helicobacter, Mucispirillum, Enterorhabdus). Altogether, ART, ARTs, and ARTe exhibited distinct effects on the regulation of glucose metabolism, depending on the nutritional context, and these effects were closely associated with modifications in gut microbiota composition.
PubMed: 38866191
DOI: 10.1016/j.jnutbio.2024.109687 -
Poultry Science May 2024Campylobacter jejuni continues to be a major public health issue worldwide. Poultry are recognized as the main reservoir for this foodborne pathogen. Implementing...
Campylobacter jejuni continues to be a major public health issue worldwide. Poultry are recognized as the main reservoir for this foodborne pathogen. Implementing measures to decrease C. jejuni colonization on farms has been regarded as the most effective strategy to control the incidence of campylobacteriosis. The probiotics supplementation has been regarded as an attractive approach against C. jejuni in chickens. Here the inhibitory effects of one probiotic B. velezensis isolate CAU277 against C. jejuni was evaluated in vitro and in vivo. The in vitro antimicrobial activity showed that the supernatant of B. velezensis exhibited the most pronounced inhibitory effects on Campylobacter strains compared to other bacterial species. When co-cultured with B. velezensis, the growth of C. jejuni reduced significantly from 7.46 log CFU/mL (24 h) to 1.02 log CFU/mL (48 h). Further, the antimicrobial activity of B. velezensis against C. jejuni remained stable under a broad range of temperature, pH, and protease treatments. The in vivo experiments demonstrated that oral administration of B. velezensis significantly reduced the colonization of C. jejuni by 2.0 log CFU/g of feces in chicken cecum at 15 d postinoculation. In addition, the supplementary of B. velezensis significantly increased microbial species richness and diversity in chicken ileum, especially enhanced the bacterial population of Alistipes and Christensenellaceae, and decreased the existence of Lachnoclostridium. Our study presents that B. velezensis possesses antimicrobial activities against C. jejuni and promotes microbiota diversity in chicken intestines. These findings indicate a potential to develop an effective probiotic additive to control C. jejuni infection in chicken.
PubMed: 38865770
DOI: 10.1016/j.psj.2024.103897 -
Transplant Immunology Jun 2024Sepsis has a high incidence, morbidity, and mortality rate and is a great threat to human safety. Gut health plays an important role in sepsis development. Qi Huang Fang...
OBJECTIVE
Sepsis has a high incidence, morbidity, and mortality rate and is a great threat to human safety. Gut health plays an important role in sepsis development. Qi Huang Fang (QHF) contains astragalus, rhubarb, zhishi, and atractylodes. It is used to treat syndromes of obstructive qi and deficiency of righteousness. This study aimed to investigate whether QHF improves intestinal barrier function and microorganisms in mice through NLRP3 inflammatory vesicle-mediated cellular focal death.
METHODS
A mouse model of sepsis was constructed by cecal ligation and puncture (CLP) of specific pathogen-free (SPF)-grade C57BL/6 mice after continuous gavage of low, medium, and high doses of astragalus formula or probiotics for 4 weeks. Twenty-four hours postoperatively, the mechanism of action of QHF in alleviating septic intestinal dysfunction and restoring intestinal microecology, thereby alleviating intestinal injury, was evaluated by pathological observation, immunohistochemistry, western blotting, ELISA, and 16S rDNA high-throughput sequencing.
RESULTS
Different doses of QHF and probiotics ameliorated intestinal injury and reduced colonic apoptosis in mice to varying degrees (P < 0.05). Meanwhile, different doses of QHF and probiotics were able to reduce the serum levels of IL-6, IL-1β, and TNF-α (P < 0.05); down-regulate the protein expression of NLRP3, caspase-1, and caspase-11 (P < 0.05); and up-regulate the protein expression of zonula occluden-1 (ZO-1) and occludin (P < 0.05), which improved the intestinal barrier function in mice. In addition, QHF decreased the relative abundance of harmful bacteria (Firmicutes, Muribaculaceae, Campilobacterota, Helicobacter, and Alistipes) and increased the relative abundance of beneficial bacteria (Bacteroidetes and Actinobacteria) (P < 0.05).
CONCLUSION
QHF improves intestinal barrier function and gut microbiology in mice via NLRP3 inflammasome-mediated cellular pyroptosis.
PubMed: 38857634
DOI: 10.1016/j.trim.2024.102072 -
Microbial Biotechnology Jun 2024Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current...
Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.
Topics: Gastrointestinal Microbiome; Animals; Grape Seed Extract; Mice; Female; Estrogens; Lipid Metabolism; Dysbiosis; Mice, Inbred C57BL; Bacteria; Osteoporosis; Disease Models, Animal; Adipose Tissue; Ovariectomy
PubMed: 38850270
DOI: 10.1111/1751-7915.14485 -
Health Psychology Research 2024In the latest research, the concept of stress is associated with the deregulation of several biological systems sensitive to stress, such as the immune system, the...
In the latest research, the concept of stress is associated with the deregulation of several biological systems sensitive to stress, such as the immune system, the microbiome, the endocrine system and neuroanatomical substrates. The objective of the research was to identify the fecal microbiome in patients diagnosed with chronic stress and in healthy patients through a metabarcoding analysis. The methodology used fecal samples collected from 20 patients with stress and 20 healthy patients. For the diagnosis of stress, psychological tools previously validated by external researchers were used. For metabarcoding analysis, metagenomic DNA extraction was performed from the fecal samples. Next Generation Illumina genetic sequencing targeting the 16S rDNA gene was then performed, followed by bioinformatic analysis using QUIME II software. The results, at the psychological test level, 20 people with chronic stress were diagnosed, on the other hand, at the metabarcoding level, specifically at the Gender level, the Asteroleplasma bacteria present only in the 20 healthy patients was molecularly identified. On the other hand, the bacteria Alistipes and Bifidobacterium were identified with greater predominance in the 20 patients with stress. Concluding, the bacteria Alistipes and Bifidobacterium are candidates as possible markers of the intestinal microbiome in patients with chronic stress, and the bacteria Asteroleplasma are candidates as a bacterial marker of the intestinal microbiome in healthy people. Finally, the identification of the microbiome in patients with stress opens a new path to understanding stress and its relationship to dysregulation with the microbiome.
PubMed: 38846338
DOI: 10.52965/001c.117647 -
Heliyon Jun 2024Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the...
Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the development of Chronic Obstructive Pulmonary Disease (COPD) and identified microbial biomarkers for acute exacerbations of COPD (AECOPD). Fecal samples were collected from 30 patients with stable COPD, 30 patients with AECOPD, and 10 healthy individuals. Fecal microbiological profiles were analyzed using 16S rRNA gene sequencing. The results showed a distinct difference in the bacterial community composition between the AECOPD, COPD, and healthy control groups. The COPD and AECOPD groups had higher levels of Firmicutes but lower levels of Bacteroidetes compared to the healthy control group at the phylum level. At the genus level, there was an increased abundance of Lachnoclostridium, Alistipes, Streptococcus, and Prevotella in COPD and AECOPD patients. Increasing levels of Lachnoclostridium and Prevotella may indicate an acute exacerbation of COPD. This study identified specific microbial biomarkers associated with AECOPD and characterized the composition of gut microbiota in patients with AECOPD.
PubMed: 38845997
DOI: 10.1016/j.heliyon.2024.e31512 -
Microbes and Infection Jun 2024The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with...
The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures. (www.clinicaltrials.gov: NCT04236843).
PubMed: 38843950
DOI: 10.1016/j.micinf.2024.105372 -
Gut Microbes 2024Comensal () and are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic...
Comensal () and are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in remain unclear. By using the classical lipopolysaccharide/O-antigen ' operon' in as a surface antigen model (5-gene-cluster ), and a recent typing strategy for strain classification, we characterized the integrity and conservancy of the entire operon in . Through exploratory analysis of complete genomes and metagenomes, we discovered that most have the operon fragmented into nonrandom patterns of gene-singlets and doublets/triplets, termed 'gene-clusters', or rfb-'minioperons' if predicted as transcriptional. To reflect global operon integrity, contiguity, duplication, and fragmentation principles, we propose a six-category (infra/supra-numerary) cataloging system and a Global Operon Profiling System for bacteria. Mechanistically, genomic sequence analyses revealed that operon fragmentation is driven by intra-operon insertions of predominantly -DNA () and likely natural selection in gut-wall specific micro-niches or micropathologies. -insertions, also detected in other antigenic operons (fimbriae), but not in operons deemed essential (ribosomal), could explain why have fewer KEGG-pathways despite large genomes. DNA insertions, overrepresenting DNA-exchange-avid () species, impact our interpretation of functional metagenomics data by inflating by inflating gene-based pathway inference and by overestimating 'extra-species' abundance. Of disease relevance, species isolated from cavitating/cavernous fistulous tract (CavFT) microlesions in Crohn's Disease have supra-numerary fragmented operons, stimulate TNF-alpha from macrophages with low potency, and do not induce hyperacute peritonitis in mice compared to CavFT . The impact of 'foreign-DNA' insertions on pro-inflammatory operons, metagenomics, and commensalism/opportunism requires further studies to elucidate their potential for novel diagnostics and therapeutics, and to elucidate the role of co-existing pathobionts in Crohn's disease microlesions.
Topics: Operon; Mice; Gastrointestinal Microbiome; Animals; Humans; Metagenomics; Crohn Disease; Bacteroidetes; Antigens, Bacterial; Genome, Bacterial; Enterobacteriaceae
PubMed: 38841888
DOI: 10.1080/19490976.2024.2350150 -
Biomarker Research Jun 2024Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary...
BACKGROUND
Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.
METHODS
This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored.
RESULTS
Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy.
CONCLUSIONS
Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.
PubMed: 38831368
DOI: 10.1186/s40364-024-00607-8