Pub Date : 2025-06-16DOI: 10.1163/18762891-bja00083
Y Liu, J Wang, Y Gao, Z Wang, C Zhu, F Xu, Y Chen
Aim: this study explored the impact of BLa80 (Bifidobacterium animalis subsp. lactis) and LRa05 (Lacticaseibacillus rhamnosus) on the gut microbiota composition and metabolic indicators of volunteers with alcohol-consuming habits.
Methods: in this randomised, placebo-controlled trial, we assessed the impacts of a probiotic complex containing BLa80 and LRa05 (BLC) on the gut microbiota, short-chain fatty acids (SCFAs), alanine transaminase (ALT), aspartate aminotransferase (AST) and uric acid levels in healthy participants. A total of 112 subjects were randomly assigned to receive either a placebo (maltodextrin) or the intervention (maltodextrin + BLC at 20 billion colony-forming units/day) for eight weeks. Gut microbiota alterations were monitored via 16S rRNA gene sequencing, while fecal SCFAs were quantified via gas chromatography-mass spectrometry (GC-MS). Key metabolic indicators, including ALT, AST, and uric acid, were also measured.
Results: BLC intervention maintained the gut microbiota composition in participants with alcohol consumption habits, notably increasing the abundance of beneficial genera such as Blautia, Faecalibacterium, and Subdoligranulum. Significant alterations were observed in the levels of acetic acid, valeric acid, and total SCFAs, suggesting a favourable influence on gut health and metabolic function. Furthermore, BLC showed potential for improving serum uric acid levels.
Conclusion: supplementation with BLC appears to beneficially modulate the composition of the gut microbiota, aiding in the management of alcohol-related gastrointestinal disturbances and dependency. These findings highlight BLC's potential as a therapeutic adjunct for alcohol-induced gut dysbiosis, offering a non-pharmacological strategy to mitigate metabolic risks and improve gut barrier integrity in individuals with chronic alcohol consumption. This intervention may significantly contribute to gut health improvement.
{"title":"Impact of Bifidobacterium animalis subsp. lactis BLa80 and Lacticaseibacillus rhamnosus LRa05 supplementation on the gut microbiota and metabolic health of alcohol-consuming individuals: a randomised, double-blind, placebo-controlled trial.","authors":"Y Liu, J Wang, Y Gao, Z Wang, C Zhu, F Xu, Y Chen","doi":"10.1163/18762891-bja00083","DOIUrl":"10.1163/18762891-bja00083","url":null,"abstract":"<p><strong>Aim: </strong>this study explored the impact of BLa80 (Bifidobacterium animalis subsp. lactis) and LRa05 (Lacticaseibacillus rhamnosus) on the gut microbiota composition and metabolic indicators of volunteers with alcohol-consuming habits.</p><p><strong>Methods: </strong>in this randomised, placebo-controlled trial, we assessed the impacts of a probiotic complex containing BLa80 and LRa05 (BLC) on the gut microbiota, short-chain fatty acids (SCFAs), alanine transaminase (ALT), aspartate aminotransferase (AST) and uric acid levels in healthy participants. A total of 112 subjects were randomly assigned to receive either a placebo (maltodextrin) or the intervention (maltodextrin + BLC at 20 billion colony-forming units/day) for eight weeks. Gut microbiota alterations were monitored via 16S rRNA gene sequencing, while fecal SCFAs were quantified via gas chromatography-mass spectrometry (GC-MS). Key metabolic indicators, including ALT, AST, and uric acid, were also measured.</p><p><strong>Results: </strong>BLC intervention maintained the gut microbiota composition in participants with alcohol consumption habits, notably increasing the abundance of beneficial genera such as Blautia, Faecalibacterium, and Subdoligranulum. Significant alterations were observed in the levels of acetic acid, valeric acid, and total SCFAs, suggesting a favourable influence on gut health and metabolic function. Furthermore, BLC showed potential for improving serum uric acid levels.</p><p><strong>Conclusion: </strong>supplementation with BLC appears to beneficially modulate the composition of the gut microbiota, aiding in the management of alcohol-related gastrointestinal disturbances and dependency. These findings highlight BLC's potential as a therapeutic adjunct for alcohol-induced gut dysbiosis, offering a non-pharmacological strategy to mitigate metabolic risks and improve gut barrier integrity in individuals with chronic alcohol consumption. This intervention may significantly contribute to gut health improvement.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"11-27"},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-06DOI: 10.1163/18762891-bja00081
C Wiegers, S Doğan, M Metzelaar, O F A Larsen
With our increasing lifespan comes an increasing prevalence of age-related neurological diseases, which are often difficult to treat. The gut-brain axis may provide opportunities for cognitive health improvement through gut microbiota-targeting interventions, such as probiotics. The aim of this meta-analysis is to determine the clinical potential of probiotics for the amelioration of cognitive functioning in older adults. Systematic searches were executed in PubMed, Scopus, and Web of Science to retrieve published records of randomised controlled trials (RCTs). Records were assessed to fit the criteria of focusing on probiotic supplementation with cognitive functioning as the main outcome. After screening and assessment of 56 identified records, 20 RCTs were included for analysis. Reported means and standard deviations of cognitive test scores were used to calculate standardised mean differences (SMD) with a random effects model. Where applicable, blood concentrations of pro-inflammatory cytokines were taken as a secondary outcome. Based on the calculated SMDs it appears, overall, that supplementation of probiotics tends to have positive effects on both cognitive performance and reduction of inflammatory markers in older adults, albeit not significant (SMD [95%CI] = 0.19 [-0.13, 0.52] for cognitive performance, and SMD [95%CI] = -0.44 [-0.94, 0.06] for inflammation). The set of RCTs studied here is characterised by high heterogeneity, preventing the determination of a true overall effect size.
{"title":"The role of probiotics in the improvement of cognitive performance of older adults: a meta-analysis.","authors":"C Wiegers, S Doğan, M Metzelaar, O F A Larsen","doi":"10.1163/18762891-bja00081","DOIUrl":"10.1163/18762891-bja00081","url":null,"abstract":"<p><p>With our increasing lifespan comes an increasing prevalence of age-related neurological diseases, which are often difficult to treat. The gut-brain axis may provide opportunities for cognitive health improvement through gut microbiota-targeting interventions, such as probiotics. The aim of this meta-analysis is to determine the clinical potential of probiotics for the amelioration of cognitive functioning in older adults. Systematic searches were executed in PubMed, Scopus, and Web of Science to retrieve published records of randomised controlled trials (RCTs). Records were assessed to fit the criteria of focusing on probiotic supplementation with cognitive functioning as the main outcome. After screening and assessment of 56 identified records, 20 RCTs were included for analysis. Reported means and standard deviations of cognitive test scores were used to calculate standardised mean differences (SMD) with a random effects model. Where applicable, blood concentrations of pro-inflammatory cytokines were taken as a secondary outcome. Based on the calculated SMDs it appears, overall, that supplementation of probiotics tends to have positive effects on both cognitive performance and reduction of inflammatory markers in older adults, albeit not significant (SMD [95%CI] = 0.19 [-0.13, 0.52] for cognitive performance, and SMD [95%CI] = -0.44 [-0.94, 0.06] for inflammation). The set of RCTs studied here is characterised by high heterogeneity, preventing the determination of a true overall effect size.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"615-629"},"PeriodicalIF":3.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1163/18762891-bja00072
A LeMoire, R Replogle, L Shinn, A Kamil, L Lin, A P Kuttenkeuler, J Baisley, J Wang, S-A Girard, S Recker, A Bier
Digestive health issues, including irregular bowel movements (BM) and gastrointestinal (GI) symptoms, affect millions of people in the United States and are associated with higher risks of various diseases. This randomized, double-blind, placebo-controlled study investigated the potential of Bacillus coagulans Unique IS2 to improve stool characteristics and reduce GI symptoms. Following a 2-week run-in, 144 healthy adults were randomized in a 1:1 ratio to either B. coagulans Unique IS2 (2 billion colony forming units/day) or placebo for 4 weeks. Participants were included if they had an average weekly complete spontaneous bowel movement (SBM) of ≥3.0 and <7.0 during the run-in. The primary outcome was the change in BM frequency after 4 weeks. Secondary outcomes included change in stool consistency (assessed by the Bristol Stool Form Scale), GI symptoms and quality of life, gut microbiota composition, and the proportion of complete SBM to total BM. Safety was assessed by vital signs and reports of adverse events. After 4 weeks of supplementation with Unique IS2, there was a significant increase in BM frequency ( P = 0.037). Stool consistency significantly improved after each week in the Unique IS2 group (all P < 0.05) and was significantly improved compared to a placebo after 4 weeks ( P = 0.018), driven by a significant improvement in the incidence of hard stool ( P = 0.001). There was no effect of Unique IS2 supplementation on GI symptoms and quality of life (Gastrointestinal Quality of Life Index), gut microbiota composition (analysis of stool samples by 16S rRNA), or proportion of complete SBM to total BM. Unique IS2 was safe and well tolerated over the 4 weeks of supplementation. Our results suggest that B. coagulans Unique IS2 is a promising strategy to improve stool characteristics of individuals with hard stools and poor stool quality. Clinicaltrials.gov registration: NCT05123664.
{"title":"Bacillus coagulans Unique IS2 improves stool characteristics in healthy adults with infrequent bowel movements: a randomized, double-blind, placebo-controlled trial.","authors":"A LeMoire, R Replogle, L Shinn, A Kamil, L Lin, A P Kuttenkeuler, J Baisley, J Wang, S-A Girard, S Recker, A Bier","doi":"10.1163/18762891-bja00072","DOIUrl":"10.1163/18762891-bja00072","url":null,"abstract":"<p><p>Digestive health issues, including irregular bowel movements (BM) and gastrointestinal (GI) symptoms, affect millions of people in the United States and are associated with higher risks of various diseases. This randomized, double-blind, placebo-controlled study investigated the potential of Bacillus coagulans Unique IS2 to improve stool characteristics and reduce GI symptoms. Following a 2-week run-in, 144 healthy adults were randomized in a 1:1 ratio to either B. coagulans Unique IS2 (2 billion colony forming units/day) or placebo for 4 weeks. Participants were included if they had an average weekly complete spontaneous bowel movement (SBM) of ≥3.0 and <7.0 during the run-in. The primary outcome was the change in BM frequency after 4 weeks. Secondary outcomes included change in stool consistency (assessed by the Bristol Stool Form Scale), GI symptoms and quality of life, gut microbiota composition, and the proportion of complete SBM to total BM. Safety was assessed by vital signs and reports of adverse events. After 4 weeks of supplementation with Unique IS2, there was a significant increase in BM frequency ( P = 0.037). Stool consistency significantly improved after each week in the Unique IS2 group (all P < 0.05) and was significantly improved compared to a placebo after 4 weeks ( P = 0.018), driven by a significant improvement in the incidence of hard stool ( P = 0.001). There was no effect of Unique IS2 supplementation on GI symptoms and quality of life (Gastrointestinal Quality of Life Index), gut microbiota composition (analysis of stool samples by 16S rRNA), or proportion of complete SBM to total BM. Unique IS2 was safe and well tolerated over the 4 weeks of supplementation. Our results suggest that B. coagulans Unique IS2 is a promising strategy to improve stool characteristics of individuals with hard stools and poor stool quality. Clinicaltrials.gov registration: NCT05123664.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"533-543"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-21DOI: 10.1163/18762891-bja00080
L Wu, J-H Wang, S-H Park, Y Cui, K Han, H Kim
Recently, Bacteroides species, a dominant genus of commensal gut bacteria, have been increasingly recognised as potential next-generation postbiotics. The present study isolated nine Bacteroides POTENTIAL postbiotics from healthy human feces. Among them, Phocaeicola vulgatus (PV-1), Bacteroides thetaiotaomicron (BT-1), and Bacteroides uniformis (BU-1) were selected based on their capacity to inhibit lipogenesis and their potential synergy in vitro. Subsequently, the anti-obesity effect of the three Bacteroides postbiotics was comparatively investigated, both in combination (VTU) and individually, using a high-fat diet (HFD)-fed mouse model. VTU more notably reduced HFD-triggered excessive body mass, fat, and liver weights compared to the individual postbiotics. Additionally, VTU markedly attenuated serum triglyceride, total cholesterol, fasting blood glucose, and insulin levels compared to the HFD-alone treatment. Furthermore, VTU significantly downregulated the expression of lipogenesis-associated genes in the liver, including PPARγ, C/EBPα, AP2, CD36, FAS, ACC1, and LDLR, while upregulating beige-specific marker genes in the white adipose tissue, such as PRDM16, UCP1, and PPARγ. Moreover, VTU significantly altered the serum metabolomic profile, significantly changing several metabolites like lysophosphatidylcholines (LPCs) and Boc-homoglutamic acid. These findings indicate that the combination of PV-1, BU-1, and BT-1 synergistically ameliorated obesity by regulating lipid and glucose metabolism. Hence, we propose that Bacteroides postbiotics, including their combinations, could be developed as novel therapeutic agents for alleviating obesity and its complications in the future.
{"title":"Synergistic effects of human-origin novel postbiotic Bacteroides & Phocaeicola on obesity and thermogenesis in high-fat diet-induced metabolic dysfunction.","authors":"L Wu, J-H Wang, S-H Park, Y Cui, K Han, H Kim","doi":"10.1163/18762891-bja00080","DOIUrl":"10.1163/18762891-bja00080","url":null,"abstract":"<p><p>Recently, Bacteroides species, a dominant genus of commensal gut bacteria, have been increasingly recognised as potential next-generation postbiotics. The present study isolated nine Bacteroides POTENTIAL postbiotics from healthy human feces. Among them, Phocaeicola vulgatus (PV-1), Bacteroides thetaiotaomicron (BT-1), and Bacteroides uniformis (BU-1) were selected based on their capacity to inhibit lipogenesis and their potential synergy in vitro. Subsequently, the anti-obesity effect of the three Bacteroides postbiotics was comparatively investigated, both in combination (VTU) and individually, using a high-fat diet (HFD)-fed mouse model. VTU more notably reduced HFD-triggered excessive body mass, fat, and liver weights compared to the individual postbiotics. Additionally, VTU markedly attenuated serum triglyceride, total cholesterol, fasting blood glucose, and insulin levels compared to the HFD-alone treatment. Furthermore, VTU significantly downregulated the expression of lipogenesis-associated genes in the liver, including PPARγ, C/EBPα, AP2, CD36, FAS, ACC1, and LDLR, while upregulating beige-specific marker genes in the white adipose tissue, such as PRDM16, UCP1, and PPARγ. Moreover, VTU significantly altered the serum metabolomic profile, significantly changing several metabolites like lysophosphatidylcholines (LPCs) and Boc-homoglutamic acid. These findings indicate that the combination of PV-1, BU-1, and BT-1 synergistically ameliorated obesity by regulating lipid and glucose metabolism. Hence, we propose that Bacteroides postbiotics, including their combinations, could be developed as novel therapeutic agents for alleviating obesity and its complications in the future.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"75-93"},"PeriodicalIF":3.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-12DOI: 10.1163/18762891-bja00079
P Xu, U Mageswary, A A Nisaa, S D Balasubramaniam, S B Samsudin, N I B M Rusdi, A R A Jerip, C E Oon, M H A Bakar, D Rajendran, J J Tan, F F Roslan, S Sreenivasan, V Balakrishnan, S B Sany, C S Tan, M T Liong
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).
人乳头瘤病毒(HPV)是导致妇女宫颈癌的主要原因之一,而目前没有治疗或干预措施来降低宫颈HPV的浓度。因此,我们的目的是研究益生菌植物乳杆菌Probio87(口服剂量为9 log CFU/天)或安慰剂对降低HPV阳性妇女阴道HPV丰度的影响。在一项平行、随机、双盲和安慰剂对照研究中,女性被随机分为益生菌组(n = 44,平均年龄41.70±1.06岁)和安慰剂组(n = 45,平均年龄41.13±1.20岁)。12周后,与安慰剂组相比,益生菌组阴道HPV丰度(P = 0.001)和纽金特评分(P < 0.001)降低。VAS和VuAS问卷调查显示,与安慰剂组相比,益生菌组在外阴干燥(P = 0.023)、疼痛(P = 0.049)、社会交往、日常活动(P < 0.05)和性活动(P = 0.022)方面均有改善。血液基因表达显示,安慰剂组促炎细胞因子(IL-1β, P = 0.006;IFN-γ, P = 0.028)和t细胞标志物(CD44, P = 0.008;Cxcr5, p = 0.040;CD4, P = 0.016)与安慰剂组相比,表明炎症增加。与益生菌组相比,安慰剂组神经营养因子BDNF和CREB表达上调(P < 0.05), IDO (P = 0.001)和TDO (P = 0.036)表达升高,提示犬尿氨酸途径活性和应激增加。总的来说,补充益生菌似乎可以减少阴道HPV的丰度,可能是通过降低炎症和增强免疫力,同时减轻HPV感染对HPV阳性妇女生活质量的负面影响。临床试验注册:ClinicalTrials.gov (NCT05316064)。
{"title":"Probiotic reduces vaginal HPV abundance, improves immunity and quality of life in HPV-positive women: a randomised, placebo-controlled and double-blind study.","authors":"P Xu, U Mageswary, A A Nisaa, S D Balasubramaniam, S B Samsudin, N I B M Rusdi, A R A Jerip, C E Oon, M H A Bakar, D Rajendran, J J Tan, F F Roslan, S Sreenivasan, V Balakrishnan, S B Sany, C S Tan, M T Liong","doi":"10.1163/18762891-bja00079","DOIUrl":"10.1163/18762891-bja00079","url":null,"abstract":"<p><p>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).</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"667-684"},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-08DOI: 10.1163/18762891-bja00078
R Levit, A de Moreno de LeBlanc, S Gontier, A Aucouturier, P Langella, L G Bermúdez-Humarán, J G LeBlanc
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.
{"title":"Production of human elafin by genetically modified Lactococcus lactis: evaluation of its anti-inflammatory effects in a murine model of intestinal mucositis.","authors":"R Levit, A de Moreno de LeBlanc, S Gontier, A Aucouturier, P Langella, L G Bermúdez-Humarán, J G LeBlanc","doi":"10.1163/18762891-bja00078","DOIUrl":"10.1163/18762891-bja00078","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"95-107"},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1163/18762891-bja00077
C E Klostermann, M Fassarella, E G Zoetendal, H A Schols
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.
{"title":"Starch-degrading gut microbes Ruminococcus bromii and Bifidobacterium adolescentis differ in their ability to degrade resistant starch type 3.","authors":"C E Klostermann, M Fassarella, E G Zoetendal, H A Schols","doi":"10.1163/18762891-bja00077","DOIUrl":"10.1163/18762891-bja00077","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"687-706"},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1163/18762891-bja00076
D Sun, J Yu, Y Zhan, X Cheng, J Zhang, Y Li, Q Li, Y Xiong, W Liu
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.
{"title":"Bifid Triple Viable Capsules alleviate constipation by modulating gut microbiota and maintaining the integrity of the intestinal epithelial barrier.","authors":"D Sun, J Yu, Y Zhan, X Cheng, J Zhang, Y Li, Q Li, Y Xiong, W Liu","doi":"10.1163/18762891-bja00076","DOIUrl":"10.1163/18762891-bja00076","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"61-74"},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1163/18762891-bja00075
D V Patangia, G Grimaud, K Lyons, E Dempsey, C A Ryan, C-A O'Shea, R P Ross, C Stanton
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.
虽然母乳喂养对婴儿肠道菌群发育的重要性已经确立,但很少有研究比较母乳喂养时间对婴儿肠道菌群发育的影响。在这项初步研究中,我们纳入了23名婴儿,分为4组,比较前4周(BreastFed_4)或8周(BreastFed_8)母乳喂养时间与纯母乳喂养(Exc breast Fed)或6个月配方奶喂养(formula Fed)的影响。我们对88份婴儿粪便样本和64份相应的母乳样本进行了宏基因组鸟枪测序,以检测微生物组成。母乳样本显示存在先前确定的核心细菌,包括葡萄球菌、链球菌、棒状杆菌、表皮杆菌、罗氏菌和假单胞菌属。我们报告说,与配方奶组相比,Exc母乳喂养婴儿组具有最低的α多样性和独特的微生物组成。BreastFed_4与所有其他组明显聚集,表明喂养时间和时间对婴儿微生物群的影响。某些双歧杆菌与某些群体的相关性更强,特别是婴儿双歧杆菌与Exc母乳喂养的相关性更强,而拟杆菌/Phocaeicola与BreastFed_8的相关性更强。Exc母乳组持续存在的频率最高,以婴儿双歧杆菌为优势持续存在,而配方奶组以双歧杆菌为优势持续存在。与非坚持者相比,坚持者在所有组的早期生活中都表现出明显更高的几种糖苷水解酶(GH)丰度。这项研究强调了婴儿肠道微生物群的变化与母乳喂养持续时间的关系,需要对母乳喂养持续时间对长期健康结果的影响进行更详细的研究。
{"title":"Influence of feeding habit and duration on infant gut microbiome - a 6 month pilot study.","authors":"D V Patangia, G Grimaud, K Lyons, E Dempsey, C A Ryan, C-A O'Shea, R P Ross, C Stanton","doi":"10.1163/18762891-bja00075","DOIUrl":"10.1163/18762891-bja00075","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"631-645"},"PeriodicalIF":3.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-24DOI: 10.1163/18762891-bja00073
A D Grant, M C B Erfe, C J Delebecque, D Keller, N P Zimmerman, P L Oliver, B Youssef, J Moos, V Luna, N Craft
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).
主要的抑制性神经递质γ -氨基丁酸或GABA在情绪和睡眠中起着关键作用。GABA在中枢神经系统和肠-脑轴中都有镇静和抗焦虑作用,这引起了人们对肠道GABA调节情绪和睡眠的潜力的兴趣。几种细菌菌株可以产生GABA,但它们对现实世界的影响却知之甚少。我们研究了2剂植物乳杆菌Lp815菌株在6周内对轻度至中度焦虑成人的焦虑、睡眠、情绪、生活质量、认知、心率变异性和不良事件的影响。该试验结构为双盲、随机、安慰剂对照试验,可选择开放标签扩展。参与者被盲目分配接受安慰剂,每天10亿菌落形成单位(CFU)或50亿CFU的口服胶囊。参与者每两周完成一次焦虑、失眠和认知测量,每日情绪、睡眠和生活质量调查,并收集可穿戴心率变异性。83例,年龄39±13岁,63%为女性,64%为白人。与安慰剂相比,接受50亿CFU治疗的参与者在第4周和第6周的焦虑(GAD-7)评分显著降低(Kruskal-Wallis P < 0.05)。这一结果具有临床意义,在50亿CFU队列中,68%的参与者在第6周的GAD-7评分中表现出不止一个类别的改善,而10亿CFU组为37%,安慰剂组为26%(例如,从中度到无焦虑)(50亿CFU vs安慰剂的Fisher精确检验P = 0.002)。未发生严重不良事件。每日服用含有50亿CFU Lp815的胶囊,可在每日服用后4周和6周显著降低不同成年人的焦虑。产生gaba的益生菌可能为轻度至中度焦虑的人提供一种安全的减少焦虑的选择。试验注册。该试验已获得IRB批准并在ClinicalTrials.gov注册(NCT06466603)。
{"title":"Lactiplantibacillus plantarum Lp815 decreases anxiety in people with mild to moderate anxiety: a direct-to-consumer, randomised, double-blind, placebo-controlled study.","authors":"A D Grant, M C B Erfe, C J Delebecque, D Keller, N P Zimmerman, P L Oliver, B Youssef, J Moos, V Luna, N Craft","doi":"10.1163/18762891-bja00073","DOIUrl":"10.1163/18762891-bja00073","url":null,"abstract":"<p><p>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).</p>","PeriodicalId":8834,"journal":{"name":"Beneficial microbes","volume":" ","pages":"521-532"},"PeriodicalIF":3.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}