Pub Date : 2024-07-18DOI: 10.3389/frmbi.2024.1432646
N. Chandel, Jeremiah Paul Gorremuchu, Vivek Thakur
The human gut microbiome harbors millions of bacterial species, including opportunistic pathogens, and this microbial community is exposed to antimicrobial agents present in food, the external environment, or drugs. Thus, it increases the risk of commensals being enriched with resistant genes, which may get even transmitted to opportunistic pathogens often with the help of mobile genetic elements. There is limited information about the current burden of resistant genes in the healthy gut microbiome of the Indian population, the latter is not only the largest in the world but is also periodically monitored for the prevalence of antibiotic resistance in clinical samples.We analyzed publicly available fecal whole-metagenome shotgun sequencing data from 141 samples from three healthy Indian cohorts for antimicrobial-resistance burden, and their likely transmission modes.The overall resistance profile showed a higher number of resistance genes against tetracycline, glycopeptide, and aminoglycoside. Out of a total of 188 antimicrobial resistance genes identified in all cohorts, moderately to highly prevalent ones could potentially target seven of the ‘reserve’ group antibiotics (colistin, fosfomycin, Polymyxin). We also observed that geographical location affected the prevalence/abundance of some of the resistance genes. The higher abundance of several tetracycline and vancomycin resistance genes in tribal cohorts compared to the other two urban locations was intriguing. Species E. coli had the highest number of resistant genes, and given its relatively modest abundance in gut microbiomes can pose a risk of becoming a hub for the horizontal transfer of resistance genes to others. Lastly, a subset of the resistance genes showed association with several types of mobile genetic elements, which potentially could facilitate their transmission within the gut community.This is a first systematic report on AMR genes in healthy gut microbiome samples from multiple locations of India. While trends for several of the prevalent AMR genes showed similarity with global data, but a few population specific trends need further attention by policy-makers. The association of AMR genes with mobile elements may pose a risk for transmission to other gut bacteria.
人体肠道微生物群中有数以百万计的细菌物种，其中包括机会性病原体，这种微生物群落会接触到食物、外部环境或药物中的抗菌剂。因此，这增加了共生菌富集耐药基因的风险，而耐药基因甚至可能在移动遗传因子的帮助下传播给机会性病原体。目前有关印度人健康肠道微生物组中耐药基因负担的信息非常有限，而印度不仅是世界上最大的肠道微生物组，而且还定期监测临床样本中抗生素耐药性的流行情况。我们分析了公开的粪便全基因组猎枪测序数据，这些数据来自三个印度健康人群的 141 份样本，目的是分析抗菌素耐药性的负担及其可能的传播模式。在所有队列中发现的总共 188 个抗菌素耐药基因中，中度到高度流行的耐药基因可能针对 7 种 "储备 "抗生素（秋水仙素、磷霉素、多粘菌素）。我们还观察到，地理位置影响了某些抗性基因的流行/丰度。与其他两个城市地区相比，部落人群中四环素和万古霉素耐药基因的含量更高，这一点很耐人寻味。大肠杆菌是耐药基因数量最多的菌种，由于它在肠道微生物组中的数量相对较少，因此有可能成为耐药基因向其他菌种横向转移的中心。最后，一部分耐药基因显示与几种类型的移动遗传因子有关，这可能会促进耐药基因在肠道群落中的传播。这是第一份关于印度多地健康肠道微生物组样本中 AMR 基因的系统性报告。虽然一些流行的 AMR 基因的趋势与全球数据相似，但一些特定人群的趋势需要决策者进一步关注。AMR 基因与移动元素的关联可能会带来向其他肠道细菌传播的风险。
{"title":"Antimicrobial resistance burden, and mechanisms of its emergence in gut microbiomes of Indian population","authors":"N. Chandel, Jeremiah Paul Gorremuchu, Vivek Thakur","doi":"10.3389/frmbi.2024.1432646","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1432646","url":null,"abstract":"The human gut microbiome harbors millions of bacterial species, including opportunistic pathogens, and this microbial community is exposed to antimicrobial agents present in food, the external environment, or drugs. Thus, it increases the risk of commensals being enriched with resistant genes, which may get even transmitted to opportunistic pathogens often with the help of mobile genetic elements. There is limited information about the current burden of resistant genes in the healthy gut microbiome of the Indian population, the latter is not only the largest in the world but is also periodically monitored for the prevalence of antibiotic resistance in clinical samples.We analyzed publicly available fecal whole-metagenome shotgun sequencing data from 141 samples from three healthy Indian cohorts for antimicrobial-resistance burden, and their likely transmission modes.The overall resistance profile showed a higher number of resistance genes against tetracycline, glycopeptide, and aminoglycoside. Out of a total of 188 antimicrobial resistance genes identified in all cohorts, moderately to highly prevalent ones could potentially target seven of the ‘reserve’ group antibiotics (colistin, fosfomycin, Polymyxin). We also observed that geographical location affected the prevalence/abundance of some of the resistance genes. The higher abundance of several tetracycline and vancomycin resistance genes in tribal cohorts compared to the other two urban locations was intriguing. Species E. coli had the highest number of resistant genes, and given its relatively modest abundance in gut microbiomes can pose a risk of becoming a hub for the horizontal transfer of resistance genes to others. Lastly, a subset of the resistance genes showed association with several types of mobile genetic elements, which potentially could facilitate their transmission within the gut community.This is a first systematic report on AMR genes in healthy gut microbiome samples from multiple locations of India. While trends for several of the prevalent AMR genes showed similarity with global data, but a few population specific trends need further attention by policy-makers. The association of AMR genes with mobile elements may pose a risk for transmission to other gut bacteria.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":" 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141826434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.
{"title":"Recent advances in fecal microbiota transplantation for Clostridium difficile infection-associated diarrhea after kidney transplantation","authors":"Yurong Li, Yaoyao Yang, Ning Yang, Qin Wu, Jinjin Yang, Jing Guo, Hongmei Zhang","doi":"10.3389/frmbi.2024.1409967","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1409967","url":null,"abstract":"Kidney transplantation is considered to be the best treatment for end-stage renal disease. To reduce the incidence of rejection and improve the survival of recipients and kidney grafts, kidney transplant recipients must take immunosuppressive agents, and some patients require them for the rest of their lifetime. These treatment regimens can result in susceptibility to opportunistic infections and disrupt the intestinal microbiota, thereby leading to diarrhea, which causes water and electrolyte metabolism disorder, nutrient malabsorption, and instability in the blood concentrations of the immunosuppressive agents. Fluctuating blood concentration levels of these agents necessitate frequent laboratory monitoring and dose adjustments to avoid poor adherence and increase the risk of graft rejection. Furthermore, severe diarrhea can cause kidney transplant failure or death. Clostridium difficile infection (CDI) is the leading cause of diarrhea after renal transplantation. Traditional antibiotics can kill C. difficile; however, spores can remain in the gut. Disruption of the intestinal flora caused by antibiotherapy increases the risk of developing recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) has been proven to be a safe and effective treatment for CDI and is recommended for rCDI owing to its convenient material acquisition method, high efficacy, and low incidence of adverse reactions. This review summarizes the recent progress in FMT for CDI-associated diarrhea after renal transplantation.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"60 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.3389/frmbi.2024.1412468
A. Kaye, Matthew Rusling, Amey Dhopeshwarkar, Parhesh Kumar, Lauren Wagment-Points, Kenneth Mackie, Li-Lian Yuan
Obesity and high-fat diets induce consistent alterations in gut microbiota composition. Observations from epidemiological reviews and experiments also illustrate weight regulation effects of delta9-tetrahydrocannabinol (THC) with microbiome shifts. Therefore, we investigated the weight-loss potential of THC in obese mice models and to elucidate the contribution of specific gut microbiome changes in THC-induced weight loss.High-fat diet induced obese mice were treated with oral THC supplementation for two weeks and compared with controls. In addition to measuring weight, fecal samples were obtained at various timepoints, sequenced for bacterial 16s rRNA content and analyzed using QIIME2. Alpha and beta diversity were computed followed by linear mixed effects (LME) modeling of bacterial relative abundance relationship to THC treatment and weight change.In both male and female mice, the THC group had significantly greater average weight loss than controls (−17.8% vs. −0.22%, p<0.001 and −13.8% vs. +2.9%, p<0.001 respectively). Male mice had 8 bacterial taxonomic features that were both significantly different in relative abundance change over time with THC and correlated with weight change. An LME model using three bacterial features explained 76% of the variance in weight change with 24% of variation explained by fixed effects of feature relative abundance alone. The model also accurately predicted weight change in a second male mouse cohort (R=0.64, R2=0.41, p=<0.001). Female mice had fewer significant predictive features and were difficult to model, but the male-produced 3-feature model still accurately predicted weight change in the females (R=0.66, R2=0.44, p<0.001).Using a stepwise feature selection approach, our results indicate that sex-specific gut microbiome composition changes play some role in THC-induced weight loss. Additionally, we illustrated the concept of microbiome feature-based modeling to predict weight changes.
{"title":"Microbiome variations induced by delta9-tetrahydrocannabinol predict weight reduction in obese mice","authors":"A. Kaye, Matthew Rusling, Amey Dhopeshwarkar, Parhesh Kumar, Lauren Wagment-Points, Kenneth Mackie, Li-Lian Yuan","doi":"10.3389/frmbi.2024.1412468","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1412468","url":null,"abstract":"Obesity and high-fat diets induce consistent alterations in gut microbiota composition. Observations from epidemiological reviews and experiments also illustrate weight regulation effects of delta9-tetrahydrocannabinol (THC) with microbiome shifts. Therefore, we investigated the weight-loss potential of THC in obese mice models and to elucidate the contribution of specific gut microbiome changes in THC-induced weight loss.High-fat diet induced obese mice were treated with oral THC supplementation for two weeks and compared with controls. In addition to measuring weight, fecal samples were obtained at various timepoints, sequenced for bacterial 16s rRNA content and analyzed using QIIME2. Alpha and beta diversity were computed followed by linear mixed effects (LME) modeling of bacterial relative abundance relationship to THC treatment and weight change.In both male and female mice, the THC group had significantly greater average weight loss than controls (−17.8% vs. −0.22%, p<0.001 and −13.8% vs. +2.9%, p<0.001 respectively). Male mice had 8 bacterial taxonomic features that were both significantly different in relative abundance change over time with THC and correlated with weight change. An LME model using three bacterial features explained 76% of the variance in weight change with 24% of variation explained by fixed effects of feature relative abundance alone. The model also accurately predicted weight change in a second male mouse cohort (R=0.64, R2=0.41, p=<0.001). Female mice had fewer significant predictive features and were difficult to model, but the male-produced 3-feature model still accurately predicted weight change in the females (R=0.66, R2=0.44, p<0.001).Using a stepwise feature selection approach, our results indicate that sex-specific gut microbiome composition changes play some role in THC-induced weight loss. Additionally, we illustrated the concept of microbiome feature-based modeling to predict weight changes.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.3389/frmbi.2024.1416055
Sarah Pitell, Cheolwoon Woo, Evan Trump, Sarah Haig
Low-flow showerheads offer consumers economic and water-saving benefits, yet their use may inadvertently affect the microbial content of produced water and water-associated aerosols. This study aimed to compare the abundance and microbial composition of bacteria in shower water and associated respirable aerosols produced by various low flow rate (1, 1.5, and 1.8 gpm) showerheads. Our findings indicate that the lowest-flow showerhead produces water with lower total microbial and opportunistic bacterial pathogen densities compared to higher low flow rate counterparts. However, microbiome analysis revealed that 1.8 gpm flow rate showerheads exhibit reduced abundance of Gram-negative organisms and common biofilm-forming organisms, suggesting potentially lower pathogenicity compared to 1 and 1.5 gpm low-flow showerheads. Additionally, the number of respirable aerosols produced by showerheads as well as the partitioning of certain microorganisms from the water to aerosol phases was negatively correlated with flow rate, suggesting that there may be increasing exposure potential to pathogenic bioaerosols when using a 1gpm showerhead compared to a 1.8 gpm showerhead. However, the 1.5 gpm showerhead seemed to balance microbial partitioning, aerosol generation, and water conservation. Moreover, the microbial composition of aerosols produced from shower water was more influenced by the age of the showerhead than the flow rate, highlighting the significance of biofilm formation on the microbial community. Overall, our findings underscore the importance of evaluating the microbial risk associated with low-flow showerheads using multiple metrics in both water and aerosols, and dynamically assessing this over time, to ensure accurate future risk assessment.
{"title":"Balancing water conservation and health: do water-saving showerheads impact the microbes we breathe in during showering?","authors":"Sarah Pitell, Cheolwoon Woo, Evan Trump, Sarah Haig","doi":"10.3389/frmbi.2024.1416055","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1416055","url":null,"abstract":"Low-flow showerheads offer consumers economic and water-saving benefits, yet their use may inadvertently affect the microbial content of produced water and water-associated aerosols. This study aimed to compare the abundance and microbial composition of bacteria in shower water and associated respirable aerosols produced by various low flow rate (1, 1.5, and 1.8 gpm) showerheads. Our findings indicate that the lowest-flow showerhead produces water with lower total microbial and opportunistic bacterial pathogen densities compared to higher low flow rate counterparts. However, microbiome analysis revealed that 1.8 gpm flow rate showerheads exhibit reduced abundance of Gram-negative organisms and common biofilm-forming organisms, suggesting potentially lower pathogenicity compared to 1 and 1.5 gpm low-flow showerheads. Additionally, the number of respirable aerosols produced by showerheads as well as the partitioning of certain microorganisms from the water to aerosol phases was negatively correlated with flow rate, suggesting that there may be increasing exposure potential to pathogenic bioaerosols when using a 1gpm showerhead compared to a 1.8 gpm showerhead. However, the 1.5 gpm showerhead seemed to balance microbial partitioning, aerosol generation, and water conservation. Moreover, the microbial composition of aerosols produced from shower water was more influenced by the age of the showerhead than the flow rate, highlighting the significance of biofilm formation on the microbial community. Overall, our findings underscore the importance of evaluating the microbial risk associated with low-flow showerheads using multiple metrics in both water and aerosols, and dynamically assessing this over time, to ensure accurate future risk assessment.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"33 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyperuricaemia (HUA), one of chronic diseases, has an increased prevalence and is related to diseases such as gout, arthritis, infectious diseases, etc. Antimicrobial resistance (AMR) in the gut is considered as an atypical chronic disease, and poses risk to human health. The gut microbiome has been proved to be a reservoir for AMR and play an important role in HUA patients. The microbial characteristics of the gut in individuals with HUA have been previously explored, however, the characteristics of the resistome in individuals with HUA have remained largely unexplored.Thus, we investigated the landscape of the AMR in individuals with HUA and without HUA, and the potentially influential factors in a case-control study using metagenomics-based approaches.We found that drinking juice and abnormal stool were risk factors associated with HUA. The taxonomic diversity of gut microbiota in individuals with HUA was lower than that in non-HUA individuals. Notably, a higher abundance and diversity of the resistome (entire antimicrobial resistance genes) was observed in individuals with HUA (median: 1.10 vs. 0.76, P = 0.039, U-test), especially in tetracycline resistance genes (median: 0.46 vs. 0.20, P < 0.001, U-test), which are associated with more complex mobile genetic elements (MGEs) in individuals with HUA. Furthermore, we found that a higher abundance of the resistome was positively correlated with uric acid (UA) levels and affected by several host-associated factors (mainly dietary habits). Specifically, pork consumption and the consumption of root and tuber vegetables were identified as contributing factors. We also found a higher abundance of virulence genes (VGs), mostly related to adherence, antimicrobial activity, competitive advantage, and exoenzymes, in the gut microbial community of individuals with HUA.All findings revealed higher activity of the resistome and pathogenicity of the microbiota in individuals with HUA, indicating a higher health risk in the elderly HUA population.
高尿酸血症（HUA）是慢性疾病之一，发病率越来越高，并与痛风、关节炎、传染病等疾病有关。肠道中的抗菌药耐药性（AMR）被认为是一种非典型慢性疾病，对人类健康构成风险。肠道微生物组已被证明是 AMR 的储存库，在 HUA 患者中发挥着重要作用。因此，我们在一项病例对照研究中，利用基于元基因组学的方法调查了HUA患者和非HUA患者的AMR状况，以及潜在的影响因素。我们发现，喝果汁和大便异常是与 HUA 相关的风险因素。HUA 患者肠道微生物群的分类多样性低于非 HUA 患者。值得注意的是，在HUA患者中观察到抗性基因组（整个抗菌素抗性基因）的丰度和多样性更高（中位数：1.10 vs. 0.76，P = 0.039，U检验），尤其是四环素抗性基因（中位数：0.46 vs. 0.20，P < 0.001，U检验），这与HUA患者体内更复杂的移动遗传因子（MGEs）有关。此外，我们还发现，较高的抗性基因组丰度与尿酸（UA）水平呈正相关，并受几个宿主相关因素（主要是饮食习惯）的影响。具体来说，猪肉消费和块根及块茎蔬菜消费被认为是诱因。我们还发现，在HUA患者的肠道微生物群落中，毒力基因（VGs）的丰度较高，主要与粘附性、抗菌活性、竞争优势和外酶有关。所有研究结果均显示，HUA患者的抗药性基因组活性较高，微生物群的致病性也较高，这表明HUA老年人群的健康风险较高。
{"title":"Association of resistome abundance with hyperuricaemia in elderly individuals: a metagenomics study","authors":"Zhiyang Liu, Yingbo Shen, Yulin Fu, Da Sun, Liang Li, Ziquan Lv","doi":"10.3389/frmbi.2024.1384703","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1384703","url":null,"abstract":"Hyperuricaemia (HUA), one of chronic diseases, has an increased prevalence and is related to diseases such as gout, arthritis, infectious diseases, etc. Antimicrobial resistance (AMR) in the gut is considered as an atypical chronic disease, and poses risk to human health. The gut microbiome has been proved to be a reservoir for AMR and play an important role in HUA patients. The microbial characteristics of the gut in individuals with HUA have been previously explored, however, the characteristics of the resistome in individuals with HUA have remained largely unexplored.Thus, we investigated the landscape of the AMR in individuals with HUA and without HUA, and the potentially influential factors in a case-control study using metagenomics-based approaches.We found that drinking juice and abnormal stool were risk factors associated with HUA. The taxonomic diversity of gut microbiota in individuals with HUA was lower than that in non-HUA individuals. Notably, a higher abundance and diversity of the resistome (entire antimicrobial resistance genes) was observed in individuals with HUA (median: 1.10 vs. 0.76, P = 0.039, U-test), especially in tetracycline resistance genes (median: 0.46 vs. 0.20, P < 0.001, U-test), which are associated with more complex mobile genetic elements (MGEs) in individuals with HUA. Furthermore, we found that a higher abundance of the resistome was positively correlated with uric acid (UA) levels and affected by several host-associated factors (mainly dietary habits). Specifically, pork consumption and the consumption of root and tuber vegetables were identified as contributing factors. We also found a higher abundance of virulence genes (VGs), mostly related to adherence, antimicrobial activity, competitive advantage, and exoenzymes, in the gut microbial community of individuals with HUA.All findings revealed higher activity of the resistome and pathogenicity of the microbiota in individuals with HUA, indicating a higher health risk in the elderly HUA population.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"141 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-09DOI: 10.3389/frmbi.2024.1418633
Isabel Tarrant, B. B. Finlay
With the global prevalence of allergic disease continuing to rise at an alarming rate, the need for effective and safe therapeutics is paramount. Given the critical role of the early-life microbiota on immune development, emerging research suggests the potential use of live biotherapeutic products (LBP) for the prevention and treatment of childhood allergy. However, findings are limited and inconsistent. Therefore, the present review critically evaluates the current animal and human data on the therapeutic value of LBPs in allergy, the underlying immunological mechanisms by which LBPs may mediate allergy susceptibility, limitations of the current research that need to be addressed, and future research directions. Accordingly, LBPs may protect against allergic disease through several immunological and physiological mechanisms during early-life, including regulation of Th1/Th2 balance, SCFA-induced activation of GPR41/43 and HDAC inhibition, and maturation of epithelial barrier integrity. Taken together, current findings indicate powerful immunomodulatory properties of LBPs on allergic immune response, with LBPs offering exciting potential as a novel therapeutic tool for childhood allergy. However, the efficacy of LBPs in allergy is complex and influenced by many population and methodological factors, resulting in varied therapeutic benefits. While research thus far has focused on traditional probiotic strains, greater investigation into microbial consortiums selected from the microbiota of non-allergic infants may provide greater promise as a therapeutic tool for allergic disease. Further investigation, particularly into long-term efficacy, strain-specific effects, optimal supplementation regimes, and use of multi-strain consortiums, is necessary before findings can be translated into clinical applications to tackle childhood allergic disease.
{"title":"The potential of live biotherapeutic products in allergic disease: current findings and future directions","authors":"Isabel Tarrant, B. B. Finlay","doi":"10.3389/frmbi.2024.1418633","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1418633","url":null,"abstract":"With the global prevalence of allergic disease continuing to rise at an alarming rate, the need for effective and safe therapeutics is paramount. Given the critical role of the early-life microbiota on immune development, emerging research suggests the potential use of live biotherapeutic products (LBP) for the prevention and treatment of childhood allergy. However, findings are limited and inconsistent. Therefore, the present review critically evaluates the current animal and human data on the therapeutic value of LBPs in allergy, the underlying immunological mechanisms by which LBPs may mediate allergy susceptibility, limitations of the current research that need to be addressed, and future research directions. Accordingly, LBPs may protect against allergic disease through several immunological and physiological mechanisms during early-life, including regulation of Th1/Th2 balance, SCFA-induced activation of GPR41/43 and HDAC inhibition, and maturation of epithelial barrier integrity. Taken together, current findings indicate powerful immunomodulatory properties of LBPs on allergic immune response, with LBPs offering exciting potential as a novel therapeutic tool for childhood allergy. However, the efficacy of LBPs in allergy is complex and influenced by many population and methodological factors, resulting in varied therapeutic benefits. While research thus far has focused on traditional probiotic strains, greater investigation into microbial consortiums selected from the microbiota of non-allergic infants may provide greater promise as a therapeutic tool for allergic disease. Further investigation, particularly into long-term efficacy, strain-specific effects, optimal supplementation regimes, and use of multi-strain consortiums, is necessary before findings can be translated into clinical applications to tackle childhood allergic disease.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"90 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141664193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.3389/frmbi.2024.1404353
Lance Daharsh, Saroj Chandra Lohani, A. Ramer-Tait, Qingsheng Li
Humanized mice with human-like immune systems are commonly used to study immune responses to human-specific pathogens. However, one limitation of using humanized mice is their native murine gut microbiota, which significantly differs from that in humans. Given the importance of the gut microbiome to human health, these differences may profoundly impact the ability to translate results from humanized mouse studies to humans. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We previously created double humanized mice with a functional human immune system and a stable, human-like gut microbiome. Here, we characterized the engrafted human gut bacterial microbiome in our double humanized mouse model generated by transplanting fecal material from healthy human donors into the gut of humanized mice. Analysis of bacterial microbiomes in fecal samples from double humanized mice revealed they had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, extending up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors than humanized mice. In conclusion, our study highlights the successful engraftment of human fecal microbiota in BLT humanized mice and underscores the stability of this model, offering a valuable platform for investigating the intricate interplay among the human gut microbiome, immune system, and various diseases in vivo.
{"title":"Characterization of double humanized BLT-mice with stable engraftment of a human gut bacterial microbiome","authors":"Lance Daharsh, Saroj Chandra Lohani, A. Ramer-Tait, Qingsheng Li","doi":"10.3389/frmbi.2024.1404353","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1404353","url":null,"abstract":"Humanized mice with human-like immune systems are commonly used to study immune responses to human-specific pathogens. However, one limitation of using humanized mice is their native murine gut microbiota, which significantly differs from that in humans. Given the importance of the gut microbiome to human health, these differences may profoundly impact the ability to translate results from humanized mouse studies to humans. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We previously created double humanized mice with a functional human immune system and a stable, human-like gut microbiome. Here, we characterized the engrafted human gut bacterial microbiome in our double humanized mouse model generated by transplanting fecal material from healthy human donors into the gut of humanized mice. Analysis of bacterial microbiomes in fecal samples from double humanized mice revealed they had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, extending up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors than humanized mice. In conclusion, our study highlights the successful engraftment of human fecal microbiota in BLT humanized mice and underscores the stability of this model, offering a valuable platform for investigating the intricate interplay among the human gut microbiome, immune system, and various diseases in vivo.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":" 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.3389/frmbi.2024.1366948
Jie Zhou, Jiang Gui, W. Viles, Haobin Chen, Siting Li, J. Madan, Modupe O. Coker, A. Hoen
The microbial interactions within the human microbiome are complex, and few methods are available to identify these interactions within a longitudinal microbial abundance framework. Existing methods typically impose restrictive constraints, such as requiring long sequences and equal spacing, on the data format which in many cases are violated.To identify microbial interaction networks (MINs) with general longitudinal data settings, we propose a stationary Gaussian graphical model (SGGM) based on 16S rRNA gene sequencing data. In the SGGM, data can be arbitrarily spaced, and there are no restrictions on the length of data sequences from a single subject. Based on the SGGM, EM -type algorithms are devised to compute the L1-penalized maximum likelihood estimate of MINs. The algorithms employ the classical graphical LASSO algorithm as the building block and can be implemented efficiently. Extensive simulation studies show that the proposed algorithms can significantly outperform the conventional algorithms if the correlations among the longitudinal data are reasonably high. When the assumptions in the SGGM areviolated, e.g., zero inflation or data from heterogeneous microbial communities, the proposed algorithms still demonstrate robustness and perform better than the other existing algorithms. The algorithms are applied to a 16S rRNA gene sequencing data set from patients with cystic fibrosis. The results demonstrate strong evidence of an association between the MINs and the phylogenetic tree, indicating that the genetically related taxa tend to have more/stronger interactions. These results strengthen the existing findings in literature. The proposed algorithms can potentially be used to explore the network structure in genome, metabolome etc. as well.
{"title":"Identifying stationary microbial interaction networks based on irregularly spaced longitudinal 16S rRNA gene sequencing data","authors":"Jie Zhou, Jiang Gui, W. Viles, Haobin Chen, Siting Li, J. Madan, Modupe O. Coker, A. Hoen","doi":"10.3389/frmbi.2024.1366948","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1366948","url":null,"abstract":"The microbial interactions within the human microbiome are complex, and few methods are available to identify these interactions within a longitudinal microbial abundance framework. Existing methods typically impose restrictive constraints, such as requiring long sequences and equal spacing, on the data format which in many cases are violated.To identify microbial interaction networks (MINs) with general longitudinal data settings, we propose a stationary Gaussian graphical model (SGGM) based on 16S rRNA gene sequencing data. In the SGGM, data can be arbitrarily spaced, and there are no restrictions on the length of data sequences from a single subject. Based on the SGGM, EM -type algorithms are devised to compute the L1-penalized maximum likelihood estimate of MINs. The algorithms employ the classical graphical LASSO algorithm as the building block and can be implemented efficiently. Extensive simulation studies show that the proposed algorithms can significantly outperform the conventional algorithms if the correlations among the longitudinal data are reasonably high. When the assumptions in the SGGM areviolated, e.g., zero inflation or data from heterogeneous microbial communities, the proposed algorithms still demonstrate robustness and perform better than the other existing algorithms. The algorithms are applied to a 16S rRNA gene sequencing data set from patients with cystic fibrosis. The results demonstrate strong evidence of an association between the MINs and the phylogenetic tree, indicating that the genetically related taxa tend to have more/stronger interactions. These results strengthen the existing findings in literature. The proposed algorithms can potentially be used to explore the network structure in genome, metabolome etc. as well.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"38 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.3389/frmbi.2024.1399160
L. Pfavayi, E. Sibanda, Stephen Baker, M. Woolhouse, T. Mduluza, Francisca Mutapi
The human gut microbiome harbours diverse species of archaea, bacteria, fungi, protists and viruses. To date, most gut microbiome studies have focused on bacteria, neglecting other microbial communities. Consequently, less is known about the diversity and abundance of the latter. Here, we aimed to characterise the diversity and composition of protists in the gut of preschool-aged children (PSAC) in rural Zimbabwe relative to host age, sex, and schistosome infection status.The gut protist of 113 PSAC (1–5 years) was examined via shotgun metagenomic sequencing and analysed for diversity. Variation in protist abundance with host and environmental factors was analysed by permutational multivariate analysis of variance (PERMANOVA). To investigate how the composition of specific taxa varies across age, sex, nutritional measures and Schistosoma hematobium infection status, analysis of the composition of microbiomes (ANCOM) was used.Eighty protist genera were identified, and the most abundant genera detected was Blastocystis. The prevalence of pathogenic protists was comparatively low, with 12.4% and 3.4% of the participants’ gut colonised by E. histolytica and Cryptosporidium, respectively. Of all the independent variables only S. haematobium infection showed significant relationship with the structure of the gut protist, being associated with increases in Peronospora, Pseudoperonospora, Plasmopara and Blastocystis (FDR= 0.009).This study provides data on the prevalence and diversity of the gut protists in young Zimbabwean children with an emphasis on the host factors; age, sex and schistosome infection status. Our results showed no association between the host factors investigated, including anthropometric measures adjusted for age and the intestinal protist composition and structure, but S. haematobium infection status was associated with composition of specific taxa. There is a need for more studies determining how pathogenic protist interact with non-pathogenic protist in people exhibiting clinical symptoms to inform therapy and nutraceuticals.
{"title":"Diversity and composition of gut protist in young rural Zimbabwean children","authors":"L. Pfavayi, E. Sibanda, Stephen Baker, M. Woolhouse, T. Mduluza, Francisca Mutapi","doi":"10.3389/frmbi.2024.1399160","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1399160","url":null,"abstract":"The human gut microbiome harbours diverse species of archaea, bacteria, fungi, protists and viruses. To date, most gut microbiome studies have focused on bacteria, neglecting other microbial communities. Consequently, less is known about the diversity and abundance of the latter. Here, we aimed to characterise the diversity and composition of protists in the gut of preschool-aged children (PSAC) in rural Zimbabwe relative to host age, sex, and schistosome infection status.The gut protist of 113 PSAC (1–5 years) was examined via shotgun metagenomic sequencing and analysed for diversity. Variation in protist abundance with host and environmental factors was analysed by permutational multivariate analysis of variance (PERMANOVA). To investigate how the composition of specific taxa varies across age, sex, nutritional measures and Schistosoma hematobium infection status, analysis of the composition of microbiomes (ANCOM) was used.Eighty protist genera were identified, and the most abundant genera detected was Blastocystis. The prevalence of pathogenic protists was comparatively low, with 12.4% and 3.4% of the participants’ gut colonised by E. histolytica and Cryptosporidium, respectively. Of all the independent variables only S. haematobium infection showed significant relationship with the structure of the gut protist, being associated with increases in Peronospora, Pseudoperonospora, Plasmopara and Blastocystis (FDR= 0.009).This study provides data on the prevalence and diversity of the gut protists in young Zimbabwean children with an emphasis on the host factors; age, sex and schistosome infection status. Our results showed no association between the host factors investigated, including anthropometric measures adjusted for age and the intestinal protist composition and structure, but S. haematobium infection status was associated with composition of specific taxa. There is a need for more studies determining how pathogenic protist interact with non-pathogenic protist in people exhibiting clinical symptoms to inform therapy and nutraceuticals.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"61 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141110370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.3389/frmbi.2024.1399440
K. Sehgal, P. Feuerstadt
Clostridiodes difficile infection (CDI) continues to be one of the leading causes of healthcare-acquired diarrhea and infections, and recurrence is the biggest challenge in its management. As technology and research have led to a better understanding of the pathophysiology of C. difficile, we have come to appreciate the role that the gastrointestinal microbiota plays in infection onset and the prevention of recurrence. The gut microbiota is disrupted in those with CDI, which allows further propagation of the infection leading to recurrence, if the microbiota deficiency is unable to regrow itself. While antimicrobial therapy is necessary for treatment of any CDI, these therapeutics do not address the underlying disturbance of microbiota. Microbial remodulation therapies have been developed supplementing the microbiota deficiency that exists after the standard of care antimicrobial resulting in a reduction of recurrence. Fecal microbiota transplantation (FMT) was the initial attempt for this type of therapeutic and proved to be safe and effective, however never achieved FDA approval. In light of this, live biotherapeutic products (LBPs) were developed by pharmaceutical companies through a more standardized and regulated process. These products are safe and efficacious in reducing CDI recurrence when given after a standard of care antimicrobial, eventually leading to FDA approval of two products that can now be used widely in clinical practice.
{"title":"Live biotherapeutic products: a capstone for prevention of recurrent Clostridiodes difficile infection","authors":"K. Sehgal, P. Feuerstadt","doi":"10.3389/frmbi.2024.1399440","DOIUrl":"https://doi.org/10.3389/frmbi.2024.1399440","url":null,"abstract":"Clostridiodes difficile infection (CDI) continues to be one of the leading causes of healthcare-acquired diarrhea and infections, and recurrence is the biggest challenge in its management. As technology and research have led to a better understanding of the pathophysiology of C. difficile, we have come to appreciate the role that the gastrointestinal microbiota plays in infection onset and the prevention of recurrence. The gut microbiota is disrupted in those with CDI, which allows further propagation of the infection leading to recurrence, if the microbiota deficiency is unable to regrow itself. While antimicrobial therapy is necessary for treatment of any CDI, these therapeutics do not address the underlying disturbance of microbiota. Microbial remodulation therapies have been developed supplementing the microbiota deficiency that exists after the standard of care antimicrobial resulting in a reduction of recurrence. Fecal microbiota transplantation (FMT) was the initial attempt for this type of therapeutic and proved to be safe and effective, however never achieved FDA approval. In light of this, live biotherapeutic products (LBPs) were developed by pharmaceutical companies through a more standardized and regulated process. These products are safe and efficacious in reducing CDI recurrence when given after a standard of care antimicrobial, eventually leading to FDA approval of two products that can now be used widely in clinical practice.","PeriodicalId":73089,"journal":{"name":"Frontiers in microbiomes","volume":"17 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140968992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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