Beneficial microbes最新文献

The Human Papillomavirus (HPV) is one of the main causes of cervical cancer in women, while there are currently no treatment nor intervention to reduce the concentration of cervical HPV. We thus aimed to investigate the effects of a probiotic Lactiplantibacillus plantarum Probio87 (orally administered at 9 log CFU/day) or placebo for 12-weeks, on reducing the abundance of vaginal HPV in HPV-positive women. A parallel, randomised, double-blind and placebo-controlled study was performed where women were randomised to either the probiotic (n = 44, mean age 41.70 ± 1.06 years) or placebo (n = 45, mean age 41.13 ± 1.20 years). After 12 weeks, the probiotic group showed reduced vaginal HPV abundance ( P = 0.001) and Nugent scores ( P < 0.001) as compared to the placebo. VAS and VuAS questionnaires showed that the probiotic group had improved vulvar dryness ( P = 0.023), soreness ( P = 0.049), social interactions, daily activities ( P < 0.05), and sexual activity ( P = 0.022) compared to the placebo group. Blood gene expressions showed that the placebo group had higher upregulation of pro-inflammatory cytokines (IL-1β, P = 0.006; IFN-γ, P = 0.028) and T-cell markers (CD44, P = 0.008; CXCR5, P = 0.040; CD4, P = 0.016) compared to the placebo group, indicating increased inflammation. Neurotrophic factors BDNF and CREB were upregulated in the placebo group ( P < 0.05), with higher IDO ( P = 0.001) and TDO ( P = 0.036) expressions compared to the probiotic group, suggesting increased kynurenine pathway activity and stress. Overall, probiotic supplementation appeared to reduce the abundance of vaginal HPV, possibly by lowering inflammation and enhancing immunity while mitigating the negative impacts of HPV infection on quality of life in HPV-positive women. Clinical trial registration: ClinicalTrials.gov (NCT05316064).

The aim of this study was to develop a recombinant strain of Lactococcus lactis designed to produce human elafin, a serine protease inhibitor, through a Stress-Inducible Controlled Expression (SICE) System, and to evaluate its anti-inflammatory potential both in vitro and in vivo. The impact of this recombinant strain on the efficacy of 5-Fluorouracil (5-FU) was evaluated by in vitro assays with Caco-2 (human colonic cancer cells) and IEC-18 (non-cancerous intestinal cells) exposed to 5-FU with or without the recombinant bacterium. In vivo, a mouse model of intestinal mucositis (IM) was induced by daily injections of 5-FU, followed by oral administration of the recombinant strain twice daily. Key assessments included the occurrence of diarrhea, small intestinal morphology and histopathology, and serum cytokines levels. In vitro results showed that the elafin-producing strain enhanced 5-FU cytotoxicity against Caco-2 cells, while preserving IEC-18 cell viability in the presence of 5-FU. In vivo, the strain significantly reduced the occurrence of diarrhea, improved the villus height/crypt depth ratio and attenuated intestinal inflammation. In addition, the recombinant strain reduced serum levels of the pro-inflammatory cytokines IL-6 and TNF-α, while significantly increasing the anti-inflammatory cytokine IL-10. Importantly, the strain did not compromise the anti-cancer efficacy of 5-FU on tumor cells and protected non-cancer cells. These results confirm the in vivo anti-inflammatory effects of this elafin-producing strain against IM.

Intrinsic resistant starch type 3 (RS-3) is retrograded starch that is highly resistant to pancreatic digestion (≥80% RS) and will therefore transit to the colon largely intact. Two gut microbes, known as RS degraders, Ruminococcus bromii ATCC27255 and Bifidobacterium adolescentis L2-32, were studied for their ability to degrade intrinsic RS-3 with defined crystal type and chain length (A-type, degree of polymerisation (DP) 16 or DP 21; B-type, DP 32 or DP 76). Remaining glucose, malto-oligosaccharides and non-degraded insoluble RS-3 were quantified over time and remaining RS-3 was visualized by Scanning Electron Microscopy (SEM) over time and compared to degradation of granular maize and potato starch. R. bromii was not limited by any specific physico-chemical starch characteristic and degraded all substrates gradually to primarily maltose and glucose, although these sugars were not further utilised. In contrast, B. adolescentis was unable to degrade B-type intrinsic RS-3 and only slightly fermented A-type intrinsic RS-3 to acetate, whereas granular maize and potato starch were fermented readily to acetate and lactate. The extensive use of SEM in this study revealed the unique morphology of the RS-3 structures and the difference in degradation approach by the two gut microbes. It can be concluded that efficient degradation of intrinsic RS-3 requires microbes with specific enzyme machineries such as those present in R. bromii.

Constipation is a widespread gastrointestinal disorder that significantly impacts individuals' health and quality of life. Although various treatment options are available, many patients experience unsatisfactory results, creating a demand for alternative therapeutic strategies. This study explores the efficacy of Bifid Triple Viable Capsules, containing Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecium, in alleviating loperamide-induced constipation in a rat model. Rats were administered high or low doses of Bifid after induction of constipation with loperamide. Our findings demonstrate that high-dose Bifid treatment significantly improves body weight and intestinal propulsion rate in constipated rats. Histopathological analysis reveals that Bifid restores colon tissue integrity, reducing inflammation and maintaining the intestinal epithelial barrier. Using 16S rRNA sequencing, we identified an increase in the gut microbial diversity and composition, with higher levels of beneficial norank_f_norank_o_Coriobacteriales and Anaerofustis bacteria. Transcriptomic analysis of colon tissues showed that high-dose Bifid treatment modulates gene expression involved in immune system regulation and epithelial barrier integrity. Differentially expressed genes (DEGs) were enriched in pathways related to the immune response and integral component of membrane, particularly those associated with the intestinal immune network and bile acid metabolism. These results suggest that Bifid alleviates constipation by balancing the gut microbiota, regulating the gut innate immune response, and maintaining the intestinal epithelial barrier. Our study provides a foundational basis for further research and therapeutic applications of probiotics in treating gastrointestinal diseases.

While the importance of breastfeeding on the developing infant gut microbiota has been established, few studies have compared the effect of breastfeeding duration on infant gut microbiota development. In this pilot study, we included 23 infants, divided into 4 groups to compare the effect of breastfeeding duration for first 4 (BreastFed_4) or 8 weeks (BreastFed_8) compared to exclusive breast (Exc Breast Fed) or formula feeding (Formula Fed) for 6 months. We used metagenomics shotgun sequencing of 88 infant stool samples and 64 corresponding maternal milk samples to examine the microbial composition. Breast milk samples showed the presence of previously defined core bacteria including spp. belonging to Staphylococcus, Streptococcus, Corynebacterium, Cutibacterium, Rothia and Pseudomonas. We report that the Exc Breast Fed infant group had the lowest alpha diversity and a distinct microbial composition compared to the Formula Fed group. BreastFed_4 clustered distinctly from all other groups, indicating the impact of duration and time of feeding on infant microbiota. Certain Bifidobacterium spp. were more associated to certain groups, in particular, B. infantis was more associated to Exc Breast Fed while Bacteroides/Phocaeicola with BreastFed_8. Exc Breast Fed showed the highest frequency of persisters with B. infantis being the dominant persister, while B. bifidum was the dominant persister in Formula Fed group. Persisters showed significantly higher abundance of several glycoside hydrolases (GH) important in early life across all groups compared to non-persisters. This study highlights infant gut microbiota changes associated with breastfeeding duration, warranting more detailed studies on the impact of breastfeeding duration on long-term health outcomes.

The major inhibitory neurotransmitter gamma-aminobutyric acid or GABA plays a pivotal role in mood and sleep. GABA exerts sedative and anxiolytic effects both within the central nervous system and through the gut-brain axis, which has generated interest in the potential for gut GABA to modulate mood and sleep. Several bacterial strains can produce GABA, yet their real-world impacts are poorly understood. We investigated the impact of 2 doses of the strain Lactiplantibacillus plantarum Lp815 on anxiety, sleep, mood, quality of life, cognition, heart rate variability and adverse events in adults with mild to moderate anxiety over a 6-week period. The trial was structured as a double-blinded, randomised, placebo-controlled trial with optional open label extension. Participants were blindly assigned to receive either a placebo, 1 billion colony-forming units (CFU), or 5 billion CFU of the oral capsule per day. Participants completed biweekly anxiety, insomnia and cognition measures, daily mood, sleep, and quality of life surveys, and collected wearable heart rate variability. 83 individuals were evaluated, aged 39 ± 13 years, 63% female and 64% Caucasian. Participants receiving 5 billion CFU exhibited significantly lower anxiety (GAD-7) scores at weeks 4 and 6 compared to placebo (Kruskal-Wallis P < 0.05). This result was clinically meaningful, with 68% of participants in the 5 billion CFU cohort exhibiting improvement by more than one category in their GAD-7 scores at week 6, compared to 37% in the 1 billion CFU group and 26% in the placebo group (e.g. from moderate to no anxiety) (Fisher's exact test P = 0.002 for 5 billion CFU vs Placebo). No serious adverse events occurred. A daily capsule containing 5 billion CFU Lp815 significantly reduced anxiety in a diverse cohort of adults at 4 and 6 weeks following daily consumption. GABA-producing probiotics may offer a safe option for anxiety reduction in people with mild to moderate anxiety. Trial Registration. The trial was IRB approved and registered with ClinicalTrials.gov (NCT06466603).

The Traditional Asian Diet (TAD) is characterised by high dietary fibre and functional foods. This study investigated TAD's effects on meeting fibre requirements, gut microbiome, and faecal and urine metabolomes. A four-week randomised controlled trial was conducted among healthy Asian women allocated into the TAD group (n = 11) following a newly developed TAD program and the control group (n = 11). Assessments included dietary intake, gut health (symptoms, faecal form, frequency), serum fatty acids binding protein-2 (FABP-2) levels, faecal microbiome via 16s rRNA sequencing, and faecal and urine metabolites which were analysed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR), respectively. The TAD group showed significant increases in dietary fibre ( P < 0.001), reduced fat ( P < 0.05), and improved faecal form ( P = 0.009) compared to the control group. The TAD group was enriched with Parabacteroides merdae, while Bacteroides uniformis was more abundant in the control group. Individuals with baseline Prevotella copri showed its enrichment following TAD and higher butyrate levels, unlike the control group. The TAD led to lower urine levels of creatinine, dimethylamine, and phenethylamine compared to the control diet. In conclusion, the TAD program has proven beneficial effects in achieving dietary fibre, enriching the beneficial microbiota and metabolites, reducing harmful metabolites, and improving faecal form compared to a control diet. Clinical trial registration: NCT04885959, clinicaltrials.gov.

Type-2 diabetes mellitus (T2DM) is associated with a reduction of butyrate-producing gut bacteria. d-allulose and erythritol are low-no-calorie sweeteners (LNCS) used as sugar substitutes to reduce high free sugar intakes associated with non-communicable diseases, including T2DM. This is the first study to investigate the impact of representative and physiologically relevant doses of d-allulose and erythritol on the human gut microbiota of T2DM ( n = 6) and co-living healthy adults ( n = 6). Using the clinically predictive ex vivo SIFR® technology, d-allulose and erythritol were shown to significantly increase butyrate production 24-48 h after treatment and significantly increased the abundance of particular microbial families or species in both healthy individuals and those with T2DM compared to the no-substrate control (NSC). d-Allulose significantly increased the abundance of Anaerostipes hadrus and Lachnospiraceae_unclassified_species ( u _ s) at 48 h in healthy adults and adults with T2DM compared to the NSC. Erythritol significantly increased the abundance of Eubacteriaceae and Barnesiellaceae families at 48 h in healthy adults and adults with T2DM but had no significant effects on microbial species compared to the NSC. d-Allulose resulted in a larger increase in butyrate between 6-24 h whereas erythritol resulted in a larger increased butyrate between 24-48 h. The findings suggest prebiotic potential of d-allulose and erythritol worth of investigation in human clinical trials, as blending d-allulose and erythritol could be a promising strategy to reduce free sugar intakes and increase butyrate production in both healthy and T2DM individuals, resulting in beneficial effects on glycemic control.

Antibiotic treatment regimens fail to address Klebsiella pneumoniae exhibiting resistance to multiple drugs, including the last resort antibiotic, colistin. The use of probiotics as candidates for alternative antimicrobial therapy or as a source of new antibiotics is considered as an emerging trend in therapeutics. Rejuvenating the human gut with probiotics offers an intriguing therapeutic approach in various enteric diseases. However, the precise role of probiotics in non-enteric infections, particularly those caused by colistin-resistant Klebsiella pneumoniae remains unresolved, prompting further comprehensive research. Therefore, we propose an innovative prophylactic approach using Lacticaseibacilli of human gut origin against this pathogen. Probiotic characterisation like tolerance to acid, bile and sodium chloride were performed to evaluate its gastric survival. In vitro experiments revealed that non-neutralised cell-free supernatant (CFS) of Lacticaseibacillus has the potential to inhibit pathogenic K. pneumoniae. The observed growth reduction is suggestive of the cumulative effect of organic acids and other antimicrobial substances in CFS. The two Lacticaseibacillus paracasei isolates exhibited promising activity (with suspected proteinaceous heat labile molecules) against K. pneumoniae and those with better adhesion to CaCo-2 cell lines were selected for downstream studies. Scanning electron microscopic analysis of CFS treated pathogen cells revealed cell surface distortions and pore formations. The prophylactic potential of Lacticaseibacillus (live and heat-inactivated forms) in Balb/c mice model showed a reduction in histopathological and microbiological alterations caused by K. pneumoniae, when compared with untreated pathogen control. Whole genome analysis of the potential probiotic isolate revealed the genome is devoid of any antibiotic resistance genes and other virulence markers indicating its safety in vivo. Furthermore, the in vitro pathogen inhibition results were reinforced by antiSMASH and BAGEL analysis, which predicted the presence of putative bacteriocin genes. Hence, this multiapproach research study has revealed a promising prophylactic probiotic from human gut microbiome against multi-drug resistant K. pneumoniae.

The gut microbiota has a profound impact on animal physiology, improving organ function and promoting growth under different nutritional conditions. Complex mechanisms underlying growth-promotion by the gut microbiota have been described. In particular, strains of the same bacterial species within different genera exhibit strain-specific growth promotion. In a previous study, we used artificial selection on a poorly growth-promoting strain of Lactiplantibacillus plantarum (NIZO2877) and isolated evolved strains with enhanced growth-promoting capabilities in insects. However, it remains unclear to what extent existing growth-promoting strains can further optimise their benefits and whether these effects persist in well-fed mammals. Here, we experimentally evolved a Drosophila growth-promoting strain of L. plantarum (WJL) under conditions of nutrient deprivation. This strain had not undergone any prior evolutionary adaptation. Our aim was to maximize its growth-promoting benefits while evaluating the translation of this phenotype in different animal models. After artificial selection across ten Drosophila generations, we identified an evolved strain (L. plantarum IGFL1) that significantly improved Drosophila juvenile growth compared to the ancestral strain. Administration of IGFL1 to conventional C57Bl/6j male mice under both nutrient deprivation and normal dietary conditions significantly increased body length and weight growth rates compared to placebo-fed animals. These effects were comparable to those of the ancestral strain, suggesting a context-dependent phenotype. Genome sequencing of IGFL1 revealed the presence of four mutations that may be related to more effective utilization of nutrients. Our results demonstrate the high adaptive potential of L. plantarum, although functional improvements in promoting animal growth are strictly context-dependent. Despite this specificity in adaptation, both strains (the ancestral WJL and the evolved IGFL1) show transferable potential in terms of animal growth promotion, as they are both highly beneficial in flies and mice. These results pave the way for testing these strains to enhance the growth performance of agricultural target species.