Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes.
Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.
Makgeolli, a traditional Korean liquor, contains components such as lactic acid bacteria and dietary fiber, which can induce changes in the gut microbiome. Since variations in microbiome responses may exist between enterotypes-classifications based on the dominant bacterial populations in the gut-we hypothesized that the consumption of makgeolli leads to enterotype-dependent differences in gut microbial structures among healthy participants. This study aimed to determine the effect of makgeolli consumption on gut microbial structures by stratifying all participants into two enterotype groups: Bacteroides-dominant type (B-type, n = 7) and Prevotella-dominant type (P-type, n = 4). The B-type showed an increase in alpha diversity, while no significant difference was observed in the P-type following makgeolli consumption. The composition of gut microbiota significantly changed in the B-type, whereas no noticeable alteration was observed in the P-type after makgeolli consumption. Notably, Prevotella exhibited the most significant changes only in the P-type. In line with the increased abundance of Prevotella, the genes associated with carbohydrate metabolism, including pentose/glucuronate interconversions, fructose/mannose metabolism, starch/sucrose metabolism and amino sugar/nucleotide sugar metabolism were significantly enriched following makgeolli consumption in the P-type. These findings suggest that makgeolli consumption induces enterotype-dependent alterations in gut microbial composition and metabolic pathways, highlighting the potential for personalized dietary interventions.
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Myocardial infarction (MI) is a type of cardiovascular disease that influences millions of human beings worldwide and has a great rate of mortality and morbidity. Spironolactone has been used as a critical drug for the treatment of cardiac failure and it ameliorates cardiac dysfunction post-MI. Despite these findings, whether there is a relationship between the therapeutic effects of spironolactone and the gut microorganism after MI has not been determined. In our research, we used male C57BL/6 J mice to explore whether the gut microbiota mediates the beneficial function of spironolactone after myocardial infarction.
We demonstrated that deletion of the gut microbiota eliminated the beneficial function of spironolactone in MI mice, displaying exacerbated cardiac dysfunction, cardiac infarct size. In addition, the gut microbiota was altered by spironolactone after sham or MI operation in mice. We also used male C57BL/6 J mice to investigate the function of a probiotic in the myocardial infarction. In summary, our findings reveal a precious role of the gut flora in the therapeutic function of spironolactone on MI.
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2-piperidone is a crucial industrial raw material of high-value nylon-5 and nylon-6,5. Currently, a major bottleneck in the biosynthesis of 2-piperidone is the identification of highly efficient 2-piperidone synthases. In this study, we aimed to identify specific strains among 51 human gut bacterial strains capable of producing 2-piperidone and to elucidate its synthetic mechanism. Our findings revealed that four gut bacterial strains, namely Collinsella aerofaciens LFYP39, Collinsella intestinalis LFYP54, Clostridium bolteae LFYP116, and Clostridium hathewayi LFYP18, could produce 2-piperidone from 5-aminovaleric acid (5AVA).
Additionally, we observed that 2-piperidone could be synthesized from proline through cross-feeding between Clostridium difficile LFYP43 and one of the four 2-piperidone producing strains, respectively. To identify the enzyme responsible for catalyzing the conversion of 5AVA to 2-piperidone, we utilized a gain-of-function library and identified avaC (5-aminovaleric acid cyclase) in C.
intestinalis LFYP54. Moreover, homologous genes of avaC were validated in the other three bacterial strains. Notably, avaC were found to be widely distributed among environmental bacteria. Overall, our research delineated the gut bacterial strains and genes involved in 2-piperidone production, holding promise for enhancing the efficiency of industrial biosynthesis of this compound.
The human gut houses a diverse and dynamic microbiome critical for digestion, metabolism, and immune development, exerting profound efects on human health. However, these microorganisms pose a potential threat by breaching the gut barrier, entering host tissues, and triggering infections, uncontrolled infammation, and even sepsis. The intestinal epithelial cells form the primary defense, acting as a frontline barrier against microbial invasion. Antimicrobial proteins (AMPs), produced by these cells, serve as innate immune efectors that regulate the gut microbiome by directly killing or inhibiting microbes. Abnormal AMP production, whether insufcient or excessive, can disturb the microbiome equilibrium, contributing to various intestinal diseases. This review delves into the complex interactions between AMPs and the gut microbiota and sheds light on the role of AMPs in governing host-microbiota interactions. We discuss the function and mechanisms of action of AMPs, their regulation by the gut microbiota, microbial evasion strategies, and the consequences of AMP dysregulation in disease. Understanding these complex interactions between AMPs and the gut microbiota is crucial for developing strategies to enhance immune responses and combat infections within the gut microbiota. Ongoing research continues to uncover novel aspects of this intricate relationship, deepening our understanding of the factors shaping gut health. This knowledge has the potential to revolutionize therapeutic interventions, ofering enhanced treatments for a wide range of gut-related diseases.
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Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC(50)) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.
Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A-G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into the evolution of human adenoviruses and identifies genes that display high variation across the entire genome to determine recombination patterns. Hypervariable regions within genetic sequences correlate with functional characteristics, thus allowing for adaptation to new environments and hosts. Proteotyping of newly emerging and already established adenoviruses allows for prediction of the characteristics of novel viruses. HAdV-D species evolved in a direction that increased diversity through gene recombination. Bioinformatics analysis across the genome, particularly in highly variable regions, allows for the verification or re-evaluation of recombination patterns in both newly introduced and pre-existing viruses, ultimately aiding in tracing various biological traits such as virus tropism and pathogenesis. Our research does not only assist in predicting the emergence of new adenoviruses but also offers critical guidance in regard to identifying potential regulatory factors of homologous recombination hotspots.
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Due to the ever-increasing demand for meat, it has become necessary to identify cheap and sustainable sources of protein for animal feed. Feathers are the major byproduct of poultry industry, which are rich in hard-to-degrade keratin protein.
Previously we found that intact feathers can be digested into free amino acids, short peptides, and nano-/micro-keratin particles by the strain Bacillus licheniformis WHU in water, and the resulting feather hydrolysates exhibit prebiotic effects on mice. To explore the potential utilization of feather hydrolysate in the feed industry, we investigated its effects on the gut microbiota of broilers and fish. Our results suggest that feather hydrolysates significantly decrease and increase the diversity of gut microbial communities in broilers and fish, respectively. The composition of the gut microbiota was markedly altered in both of the animals. The abundance of bacteria with potentially pathogenic phenotypes in the gut microbial community of the fish significantly decreased. Staphylococcus spp., Pseudomonas spp., Neisseria spp., Achromobacter spp. were significantly inhibited by the feather hydrolysates. In addition, feather hydrolysates significantly improved proteolytic activity in the guts of broilers and fish. In fish, the expression levels of ZO-1 and TGF-α significantly improved after administration of feather hydrolysates. The results presented here suggest that feather hydrolysates generated by B. licheniformis WHU could be an alternative protein source in aquaculture and could exert beneficial effects on fish.
Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is a significant
global public health problem. Mycobacterium tuberculosis expresses a unique family of PE_PGRS proteins that have been
implicated in pathogenesis. Despite numerous studies, the functions of most PE_PGRS proteins in the pathogenesis of
mycobacterium infections remain unclear. PE_PGRS45 (Rv2615c) is only found in pathogenic mycobacteria. In this study,
we successfully constructed a recombinant Mycobacterium smegmatis (M. smegmatis) strain which heterologously expresses
the PE_PGRS45 protein. We found that overexpression of this cell wall-associated protein enhanced bacterial viability under
stress in vitro and cell survival in macrophages. MS_PE_PGRS45 decreased the secretion of pro-inflammatory cytokines such
as IL-1β, IL-6, IL-12p40, and TNF-α. We also found that MS_PE_PGRS45 increased the expression of the anti-inflammatory
cytokine IL-10 and altered macrophage-mediated immune responses. Furthermore, PE_PGRS45 enhanced the survival rate
of M. smegmatis in macrophages by inhibiting cell apoptosis. Collectively, our findings show that PE_PGRS45 is a virulent
factor actively involved in the interaction with the host macrophage.
Mycorrhizal fungi are key components of forest ecosystems and play essential roles in host health. The host specificity of
mycorrhizal fungi is variable and the mycorrhizal fungi composition for the dominant tree species is largely known but
remains unknown for the less common tree species. In this study, we collected soil samples from the roots of six understudied
ectomycorrhizal tree species from a preserved natural park in the Republic of Korea over four seasons to investigate the
host specificity of mycorrhizal fungi in multiple tree species, considering the abiotic factors. We evaluated the mycorrhizal
fungal composition in each tree species using a metabarcoding approach. Our results revealed that each host tree species
harbored unique mycorrhizal communities, despite close localization. Most mycorrhizal taxa belonged to ectomycorrhizal
fungi, but a small proportion of ericoid mycorrhizal fungi and arbuscular mycorrhizal fungi were also detected. While common
mycorrhizal fungi were shared between the plant species at the genus or higher taxonomic level, we found high host
specificity at the species/OTU (operational taxonomic unit) level. Moreover, the effects of the seasons and soil properties
on the mycorrhizal communities differed by tree species. Our results indicate that mycorrhizal fungi feature host-specificity
at lower taxonomic levels.
Norovirus (NoV) is the most common viral cause of acute gastroenteritis worldwide. Vitamin A has demonstrated the
potential to protect against gastrointestinal infections. However, the effects of vitamin A on human norovirus (HuNoV)
infections remain poorly understood. This study aimed to investigate how vitamin A administration affects NoV replication.
We demonstrated that treatment with retinol or retinoic acid (RA) inhibited NoV replication in vitro based on their effects
on HuNoV replicon-bearing cells and murine norovirus-1 (MNV-1) replication in murine cells. MNV replication in vitro
showed significant transcriptomic changes, which were partially reversed by retinol treatment. RNAi knockdown of CCL6,
a chemokine gene that was downregulated by MNV infection but upregulated by retinol administration, resulted in increased
MNV replication in vitro. This suggested a role of CCL6 in the host response to MNV infections. Similar gene expression
patterns were observed in the murine intestine after oral administration of RA and/or MNV-1.CW1. CCL6 directly decreased
HuNoV replication in HG23 cells, and might indirectly regulate the immune response against NoV infection. Finally, relative
replication levels of MNV-1.CW1 and MNV-1.CR6 were significantly increased in CCL6 knockout RAW 264.7 cells. This
study is the first to comprehensively profile transcriptomes in response to NoV infection and vitamin A treatment in vitro,
and thus may provide new insights into dietary prophylaxis and NoV infections.
Norovirus is one of the leading causes of acute gastroenteritis outbreaks worldwide. This study aimed to identify the epidemiological
characteristics of norovirus outbreaks and to provide evidence for public health entities. Specimens and epidemiological
survey data were collected to determine if there were differences in the attack rate of norovirus in terms of the
year, season, transmission route, exposure setting, and region and to determine whether there were relationships between
the reporting interval, the number of illnesses in a single outbreak and the duration of the outbreak. Norovirus outbreaks
were reported throughout the year, with seasonal characteristics (i.e., high rates in spring and winter). Among all regions in
Shenyang with the exception of Huanggu and Liaozhong, norovirus outbreaks had been reported, and the primary genotype
was GII.2[P16]. Vomiting was the most common symptom. The main places of occurrence were childcare institutions and
schools. The person-to-person route was the main transmission route. The median duration of norovirus was 3 days (IQR
[interquartile range]: 2–6 days), the median reporting interval was 2 days (IQR: 1–4 days), the median number of illnesses
in a single outbreak was 16 (IQR: 10–25); there was a positive correlation between these parameters. Norovirus surveillance
and genotyping studies still need to be further strengthened to increase knowledge regarding the pathogens and their variant
characteristics, to better characterize the patterns of norovirus outbreaks and to provide information for outbreak prevention.
Norovirus outbreaks should be detected, reported and handled early. Public health entities and the government should
develop corresponding measures for different seasons, transmission routes, exposure settings, and regions.
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We previously showed that both high-mobility group box-1 (HMGB1) and natural killer (NK) cells contribute to respiratory
syncytial virus (RSV)-induced persistent airway inflammation and airway hyperresponsiveness (AHR). Meanwhile,
Chemokine (C-X-C motif) ligand 12 (CXCL12) and its specific receptor (chemokine receptor 4, CXCR4) play important
roles in recruitment of immune cells. CXCL12 has been reported to form a complex with HMGB1 that binds to CXCR4 and
increases inflammatory cell migration. The relationship between HMGB1, NK cells and chemokines in RSV-infected model
remains unclear. An anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) was administered to observe
changes of NK cells and airway disorders in nude mice and BALB/c mice. Results showed that the mRNA expression and
protein levels of HMGB1 were elevated in late stage of RSV infection and persistent airway inflammation and AHR were
diminished after administration of anti-HMGB1 antibodies, with an associated significant decrease in CXCR4+
NK cells. In
addition, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 significantly suppressed
the recruitment of NK cells and alleviated the airway disorders. Thus, CXCL12/CXCR4 axis is involved in the recruitment
of NK cells by HMGB1, contributing to persistent airway inflammation and AHR during the late stage of RSV infection.
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The influenza A virus (IAV) has caused several pandemics,
and therefore there are many ongoing efforts to identify novel
antiviral therapeutic strategies including vaccines and antiviral
drugs. However, influenza viruses continuously undergo
antigenic drift and shift, resulting in the emergence of mutated
viruses. In turn, this decreases the efficiency of existing vaccines
and antiviral drugs to control IAV infection. Therefore,
this study sought to identify alternative therapeutic strategies
targeting host cell factors rather than viruses to avoid infection
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replication of IAV. The KIF20A increased viral protein levels in
IAV-infected cells by regulating the initial entry stage during
viral infection. Furthermore, the KIF20A inhibitor significantly
suppressed viral replication, which protected mice from morbidity
and mortality. Therefore, our findings demonstrated
that KIF20A is highly involved in the viral replication process
and viral propagation both in vitro and in vivo, and could thus
be used as a target for the development of novel antiviral drugs.
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can be continuous records representing past environments
and recognized as a time capsule of our planetary evolution.
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considered an uninhabitable ecosystem for microorganisms
to sustain their life. However, recent developments in microbiological
analysis techniques revealed the presence of unexpectedly
diverse microbial strains. Glacial microorganisms
could also provide valuable information, including not only
biological diversity and structure but also molecular systematics,
metabolic profiles, and evolutionary changes from the
past climate and ecosystem. However, there are several obstacles
in investigating the glacier environment, such as low
regional accessibility, technical difficulties of ice coring, potential
contamination during the sampling process, and low
microbial biomass. This review aims to summarize recent
knowledge on decontamination methods, biomass, diversity
based on culture-dependent and -independent methods, application
of biological proxies, greenhouse gas production
and adaptive strategies in glaciers from various regions and to
imply further directions for a comprehensive understanding
of habitatility in an icy world including outer of our planet.
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