Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA-microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.
肠道微生物组和微RNA(miRNA)在肝性脑病(HE)的发病过程中都起着一定的作用。然而,人们对粪便中微生物组和宿主衍生的 miRNA 之间的功能联系仍知之甚少。在本研究中,与慢性乙型肝炎患者相比,肝性脑病患者的肠道微生物组和粪便中的 miRNA 发生了改变。将肝性脑病患者的粪便和粪便中的 miRNA 转移给受体小鼠会加重硫代乙酰胺诱导的肝性脑病。口服 hsa-miR-7704(一种在 HE 患者粪便中高度富集的宿主来源 miRNA)会以微生物依赖的方式加重小鼠的 HE。从机制上讲,hsa-miR-7704 通过抑制 proB 来抑制长双歧杆菌的生长和粘附。长双歧杆菌及其代谢产物乙酸盐通过抑制微神经胶质细胞的活化和氨的产生来缓解 HE。我们的研究结果揭示了 miRNA-微生物组轴在 HE 中的作用,并表明粪便中的 hsa-miR-7704 是 HE 进展的潜在调节因子。
{"title":"Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy.","authors":"Yuchong Wang, Yuyu Li, Longxian Lv, Liying Zhu, Liang Hong, Xueyao Wang, Yu Zhang, Xin Wang, Hongyan Diao","doi":"10.1038/s41522-024-00487-8","DOIUrl":"10.1038/s41522-024-00487-8","url":null,"abstract":"<p><p>Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA-microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-19DOI: 10.1038/s41522-024-00482-z
Davide Bazzani, Vitor Heidrich, Paolo Manghi, Aitor Blanco-Miguez, Francesco Asnicar, Federica Armanini, Sara Cavaliere, Alberto Bertelle, Federico Dell'Acqua, Ester Dellasega, Romina Waldner, Daniela Vicentini, Mattia Bolzan, Cristiano Tomasi, Nicola Segata, Edoardo Pasolli, Paolo Ghensi
We performed a longitudinal shotgun metagenomic investigation of the plaque microbiome associated with peri-implant diseases in a cohort of 91 subjects with 320 quality-controlled metagenomes. Through recently improved taxonomic profiling methods, we identified the most discriminative species between healthy and diseased subjects at baseline, evaluated their change over time, and provided evidence that clinical treatment had a positive effect on plaque microbiome composition in patients affected by mucositis and peri-implantitis.
{"title":"Favorable subgingival plaque microbiome shifts are associated with clinical treatment for peri-implant diseases.","authors":"Davide Bazzani, Vitor Heidrich, Paolo Manghi, Aitor Blanco-Miguez, Francesco Asnicar, Federica Armanini, Sara Cavaliere, Alberto Bertelle, Federico Dell'Acqua, Ester Dellasega, Romina Waldner, Daniela Vicentini, Mattia Bolzan, Cristiano Tomasi, Nicola Segata, Edoardo Pasolli, Paolo Ghensi","doi":"10.1038/s41522-024-00482-z","DOIUrl":"10.1038/s41522-024-00482-z","url":null,"abstract":"<p><p>We performed a longitudinal shotgun metagenomic investigation of the plaque microbiome associated with peri-implant diseases in a cohort of 91 subjects with 320 quality-controlled metagenomes. Through recently improved taxonomic profiling methods, we identified the most discriminative species between healthy and diseased subjects at baseline, evaluated their change over time, and provided evidence that clinical treatment had a positive effect on plaque microbiome composition in patients affected by mucositis and peri-implantitis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-19DOI: 10.1038/s41522-024-00484-x
Melissa Soh, Ywee Chieh Tay, Co Sin Lee, Adrian Low, Laszlo Orban, Zeehan Jaafar, Henning Seedorf
Studying the gut microbes of marine fishes is an important part of conservation as many fish species are increasingly threatened by extinction. The gut microbiota of only a small fraction of the more than 32,000 known fish species has been investigated. In this study we analysed the intestinal digesta microbiota composition of more than 50 different wild fish species from tropical waters. Our results show that the fish harbour intestinal digesta microbiota that are distinct from that of the surrounding water and that location, domestication status, and host intrinsic factors are strongly associated with the microbiota composition. Furthermore, we show that the vast majority (~97%) of the fish-associated microorganisms do not have any cultured representative. Considering the impact of the microbiota on host health and physiology, these findings underpin the call to also preserve the microbiota of host species, especially those that may be exposed to habitat destruction.
{"title":"The intestinal digesta microbiota of tropical marine fish is largely uncultured and distinct from surrounding water microbiota.","authors":"Melissa Soh, Ywee Chieh Tay, Co Sin Lee, Adrian Low, Laszlo Orban, Zeehan Jaafar, Henning Seedorf","doi":"10.1038/s41522-024-00484-x","DOIUrl":"10.1038/s41522-024-00484-x","url":null,"abstract":"<p><p>Studying the gut microbes of marine fishes is an important part of conservation as many fish species are increasingly threatened by extinction. The gut microbiota of only a small fraction of the more than 32,000 known fish species has been investigated. In this study we analysed the intestinal digesta microbiota composition of more than 50 different wild fish species from tropical waters. Our results show that the fish harbour intestinal digesta microbiota that are distinct from that of the surrounding water and that location, domestication status, and host intrinsic factors are strongly associated with the microbiota composition. Furthermore, we show that the vast majority (~97%) of the fish-associated microorganisms do not have any cultured representative. Considering the impact of the microbiota on host health and physiology, these findings underpin the call to also preserve the microbiota of host species, especially those that may be exposed to habitat destruction.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-03DOI: 10.1038/s41522-024-00481-0
Audrey F. Duff, Joseph A. Jurcisek, Nikola Kurbatfinski, Tendy Chiang, Steven D. Goodman, Lauren O. Bakaletz, Michael T. Bailey
Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (n = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P < 0.05) and reductions in alpha diversity (q < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (P < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.
{"title":"Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes","authors":"Audrey F. Duff, Joseph A. Jurcisek, Nikola Kurbatfinski, Tendy Chiang, Steven D. Goodman, Lauren O. Bakaletz, Michael T. Bailey","doi":"10.1038/s41522-024-00481-0","DOIUrl":"https://doi.org/10.1038/s41522-024-00481-0","url":null,"abstract":"<p>Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable <i>Haemophilus influenzae</i> (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts (<i>n</i> = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, <i>P</i> < 0.05) and reductions in alpha diversity (<i>q</i> < 0.20) relative to baseline, mAb antibodies failed to affect diversity, indicating maintenance of a eubiotic state. Taxonomic and longitudinal analyses showed blooms in opportunistic pathogens (ANCOM) and greater magnitudes of compositional change (<i>P</i> < 0.05) following broad-spectrum antibiotic but not mAb treatments. Collectively, results showed broad-spectrum antibiotics induced significant fecal and nasopharyngeal microbiome disruption regardless of delivery route. Excitingly, biofilm-targeting antibodies had little effect on fecal and nasopharyngeal microbiomes.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fires in tropical peatlands extend to depth, transforming them from carbon sinks into methane sources and severely limit forest recovery. Peat microbiomes influence carbon transformations and forest recovery, yet our understanding of microbiome shifts post-fire is currently limited. Our previous study highlighted altered relationships between the peat surface, water table, aboveground vegetation, and methane flux after fire in a tropical peatland. Here, we link these changes to post-fire shifts in peat microbiome composition and assembly processes across depth. We report kingdom-specific and depth-dependent shifts in alpha diversity post-fire, with large differences at deeper depths. Conversely, we found shifts in microbiome composition across all depths. Compositional shifts extended to functional groups involved in methane turnover, with methanogens enriched and methanotrophs depleted at mid and deeper depths. Finally, we show that community shifts at deeper depths result from homogeneous selection associated with post-fire changes in hydrology and aboveground vegetation. Collectively, our findings provide a biological basis for previously reported methane fluxes after fire and offer new insights into depth-dependent shifts in microbiome assembly processes, which ultimately underlie ecosystem function predictability and ecosystem recovery.
{"title":"Elevated methane flux in a tropical peatland post-fire is linked to depth-dependent changes in peat microbiome assembly.","authors":"Aditya Bandla, Hasan Akhtar, Massimo Lupascu, Rahayu Sukmaria Sukri, Sanjay Swarup","doi":"10.1038/s41522-024-00478-9","DOIUrl":"10.1038/s41522-024-00478-9","url":null,"abstract":"<p><p>Fires in tropical peatlands extend to depth, transforming them from carbon sinks into methane sources and severely limit forest recovery. Peat microbiomes influence carbon transformations and forest recovery, yet our understanding of microbiome shifts post-fire is currently limited. Our previous study highlighted altered relationships between the peat surface, water table, aboveground vegetation, and methane flux after fire in a tropical peatland. Here, we link these changes to post-fire shifts in peat microbiome composition and assembly processes across depth. We report kingdom-specific and depth-dependent shifts in alpha diversity post-fire, with large differences at deeper depths. Conversely, we found shifts in microbiome composition across all depths. Compositional shifts extended to functional groups involved in methane turnover, with methanogens enriched and methanotrophs depleted at mid and deeper depths. Finally, we show that community shifts at deeper depths result from homogeneous selection associated with post-fire changes in hydrology and aboveground vegetation. Collectively, our findings provide a biological basis for previously reported methane fluxes after fire and offer new insights into depth-dependent shifts in microbiome assembly processes, which ultimately underlie ecosystem function predictability and ecosystem recovery.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-22DOI: 10.1038/s41522-023-00473-6
Hannah Greenwald Healy, Aliya Ehde, Alma Bartholow, Rose S Kantor, Kara L Nelson
Reductions in nonresidential water demand during the COVID-19 pandemic highlighted the importance of understanding how water age impacts drinking water quality and microbiota in piped distribution systems. Using benchtop model distribution systems, we aimed to characterize the impacts of elevated water age on microbiota in bulk water and pipe wall biofilms. Five replicate constant-flow reactors were fed with municipal chloraminated tap water for 6 months prior to building closures and 7 months after. After building closures, chloramine levels entering the reactors dropped; in the reactor bulk water and biofilms the mean cell counts and ATP concentrations increased over an order of magnitude while the detection of opportunistic pathogens remained low. Water age, and the corresponding physicochemical changes, strongly influenced microbial abundance and community composition. Differential initial microbial colonization also had a lasting influence on microbial communities in each reactor (i.e., historical contingency).
在 COVID-19 大流行期间,非居民用水需求的减少凸显了了解水龄如何影响饮用水水质和管道输水系统中微生物群的重要性。我们利用台式模型配水系统,旨在描述水龄升高对散装水和管壁生物膜中微生物群的影响。在建筑物关闭前的 6 个月和关闭后的 7 个月中,我们向五个重复的恒流反应器中注入了市政氯化自来水。建筑物关闭后,进入反应器的氯胺含量下降;反应器散装水和生物膜中的平均细胞数和 ATP 浓度增加了一个数量级,而机会性病原体的检出率仍然很低。水龄和相应的物理化学变化对微生物丰度和群落组成有很大影响。不同的初始微生物定植也对每个反应器中的微生物群落产生了持久的影响(即历史偶然性)。
{"title":"Responses of drinking water bulk and biofilm microbiota to elevated water age in bench-scale simulated distribution systems.","authors":"Hannah Greenwald Healy, Aliya Ehde, Alma Bartholow, Rose S Kantor, Kara L Nelson","doi":"10.1038/s41522-023-00473-6","DOIUrl":"10.1038/s41522-023-00473-6","url":null,"abstract":"<p><p>Reductions in nonresidential water demand during the COVID-19 pandemic highlighted the importance of understanding how water age impacts drinking water quality and microbiota in piped distribution systems. Using benchtop model distribution systems, we aimed to characterize the impacts of elevated water age on microbiota in bulk water and pipe wall biofilms. Five replicate constant-flow reactors were fed with municipal chloraminated tap water for 6 months prior to building closures and 7 months after. After building closures, chloramine levels entering the reactors dropped; in the reactor bulk water and biofilms the mean cell counts and ATP concentrations increased over an order of magnitude while the detection of opportunistic pathogens remained low. Water age, and the corresponding physicochemical changes, strongly influenced microbial abundance and community composition. Differential initial microbial colonization also had a lasting influence on microbial communities in each reactor (i.e., historical contingency).</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10803812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-20DOI: 10.1038/s41522-023-00472-7
Qiulin Tang, Huixi Huang, Huanji Xu, Hongwei Xia, Chenliang Zhang, Di Ye, Feng Bi
A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with Coriobacteriaceae to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that Coriobacteriaceae were enriched in the colons of HFD-fed mice. An endogenous Coriobacteriaceae strain, designated as Cori.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of Cori.ST1911 in CRC was validated in several CRC mouse models. Furthermore, Cori.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous Lactobacillus strain La.mu730 can interfere with Cori.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal Coriobacteriaceae, Cori.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC.
{"title":"Endogenous Coriobacteriaceae enriched by a high-fat diet promotes colorectal tumorigenesis through the CPT1A-ERK axis","authors":"Qiulin Tang, Huixi Huang, Huanji Xu, Hongwei Xia, Chenliang Zhang, Di Ye, Feng Bi","doi":"10.1038/s41522-023-00472-7","DOIUrl":"https://doi.org/10.1038/s41522-023-00472-7","url":null,"abstract":"<p>A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with <i>Coriobacteriaceae</i> to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that <i>Coriobacteriaceae</i> were enriched in the colons of HFD-fed mice. An endogenous <i>Coriobacteriaceae</i> strain, designated as <i>Cori</i>.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of <i>Cori</i>.ST1911 in CRC was validated in several CRC mouse models. Furthermore, <i>Cori</i>.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous <i>Lactobacillus</i> strain <i>La.mu</i>730 can interfere with <i>Cori</i>.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal <i>Coriobacteriaceae</i>, <i>Cori</i>.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139507476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-20DOI: 10.1038/s41522-024-00479-8
Tuoyu Zhou, Jingyuan Wu, Haibo Tang, Dali Liu, Byong-Hun Jeon, Weilin Jin, Yiqing Wang, Yuanzhang Zheng, Aman Khan, Huawen Han, Xiangkai Li
Probiotics hold promise as a potential therapy for colorectal cancer (CRC), but encounter obstacles related to tumor specificity, drug penetration, and dosage adjustability. In this study, genetic circuits based on the E. coli Nissle 1917 (EcN) chassis were developed to sense indicators of tumor microenvironment and control the expression of therapeutic payloads. Integration of XOR gate amplify gene switch into EcN biosensors resulted in a 1.8-2.3-fold increase in signal output, as confirmed by mathematical model fitting. Co-culturing programmable EcNs with CRC cells demonstrated a significant reduction in cellular viability ranging from 30% to 50%. This approach was further validated in a mouse subcutaneous tumor model, revealing 47%-52% inhibition of tumor growth upon administration of therapeutic strains. Additionally, in a mouse tumorigenesis model induced by AOM and DSS, the use of synthetic bacterial consortium (SynCon) equipped with multiple sensing modules led to approximately 1.2-fold increased colon length and 2.4-fold decreased polyp count. Gut microbiota analysis suggested that SynCon maintained the abundance of butyrate-producing bacteria Lactobacillaceae NK4A136, whereas reducing the level of gut inflammation-related bacteria Bacteroides. Taken together, engineered EcNs confer the advantage of specific recognition of CRC, while SynCon serves to augment the synergistic effect of this approach.
{"title":"Enhancing tumor-specific recognition of programmable synthetic bacterial consortium for precision therapy of colorectal cancer","authors":"Tuoyu Zhou, Jingyuan Wu, Haibo Tang, Dali Liu, Byong-Hun Jeon, Weilin Jin, Yiqing Wang, Yuanzhang Zheng, Aman Khan, Huawen Han, Xiangkai Li","doi":"10.1038/s41522-024-00479-8","DOIUrl":"https://doi.org/10.1038/s41522-024-00479-8","url":null,"abstract":"<p>Probiotics hold promise as a potential therapy for colorectal cancer (CRC), but encounter obstacles related to tumor specificity, drug penetration, and dosage adjustability. In this study, genetic circuits based on the <i>E. coli</i> Nissle 1917 (EcN) chassis were developed to sense indicators of tumor microenvironment and control the expression of therapeutic payloads. Integration of XOR gate amplify gene switch into EcN biosensors resulted in a 1.8-2.3-fold increase in signal output, as confirmed by mathematical model fitting. Co-culturing programmable EcNs with CRC cells demonstrated a significant reduction in cellular viability ranging from 30% to 50%. This approach was further validated in a mouse subcutaneous tumor model, revealing 47%-52% inhibition of tumor growth upon administration of therapeutic strains. Additionally, in a mouse tumorigenesis model induced by AOM and DSS, the use of synthetic bacterial consortium (SynCon) equipped with multiple sensing modules led to approximately 1.2-fold increased colon length and 2.4-fold decreased polyp count. Gut microbiota analysis suggested that SynCon maintained the abundance of butyrate-producing bacteria <i>Lactobacillaceae</i> NK4A136, whereas reducing the level of gut inflammation-related bacteria <i>Bacteroides</i>. Taken together, engineered EcNs confer the advantage of specific recognition of CRC, while SynCon serves to augment the synergistic effect of this approach.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139507568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-18DOI: 10.1038/s41522-023-00474-5
Pierre Lapaquette, Sébastien Terrat, Lil Proukhnitzky, Lucy Martine, Stéphane Grégoire, Bénédicte Buteau, Stéphanie Cabaret, Aurélie Rieu, Luis G Bermúdez-Humarán, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Olivier Berdeaux, Niyazi Acar, Marie-Agnès Bringer
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.
{"title":"Long-term intake of Lactobacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina.","authors":"Pierre Lapaquette, Sébastien Terrat, Lil Proukhnitzky, Lucy Martine, Stéphane Grégoire, Bénédicte Buteau, Stéphanie Cabaret, Aurélie Rieu, Luis G Bermúdez-Humarán, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Olivier Berdeaux, Niyazi Acar, Marie-Agnès Bringer","doi":"10.1038/s41522-023-00474-5","DOIUrl":"10.1038/s41522-023-00474-5","url":null,"abstract":"<p><p>Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}