Profiling of Intestinal Microbiota in Patients Infected with Respiratory Influenza A and B Viruses

Little is known about the association between respiratory viral infections and their impact on intestinal microbiota. Here, we compared the effect of influenza types, A and B, and influenza shedding in patients’ stools on the gut microbiota diversity and composition. Deep sequencing analysis was performed for the V4 region of the 16S rRNA gene. Fecal samples were collected from 38 adults with active respiratory influenza infection and 11 age-matched healthy controls. Influenza infection resulted in variations in intestinal bacterial community composition rather than in overall diversity. Overall, infected patients experienced an increased abundance of Bacteroidetes and a corresponding decrease in Firmicutes. Differential abundance testing illustrated that differences in gut microbiota composition were influenza type-dependent, identifying ten differentially abundant operational taxonomic units (OTUs) between influenza A- and influenza B-infected patients. Notably, virus shedding in fecal samples of some patients had significantly reduced gut bacterial diversity (p = 0.023). Further taxonomic analysis revealed that the abundance of Bacteroides fragilis was significantly higher among shedders compared to non-shedders (p = 0.037). These results provide fundamental evidence of the direct effect of influenza infection on gut microbiota diversity, as reported in patients shedding the virus.

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196 Direct comparison of human microbiota-associated (HMA) gnotobiotic piglet and mouse models

Journal of Animal Science ◽

10.1093/jas/skz122.203 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 114-115

Author(s):

Nirosh D Aluthge ◽

Wesley A Tom ◽

Alison C Bartenslager ◽

Thomas E Burkey ◽

Kelly D Heath ◽

...

Keyword(s):

Animal Models ◽

Gut Microbiota ◽

Bacterial Communities ◽

Statistical Significance ◽

Bacterial Community Composition ◽

Rrna Gene ◽

Human Donor ◽

Fecal Samples ◽

Human Microbiota ◽

Nutritional Studies

Abstract The objective of this study was to compare the establishment of human fecal bacterial communities in porcine and murine animal models. Many gut microbiota studies use human microbiota-associated (HMA) rodents as translational animal models; however, it has been questioned as to how successfully a human microbiota can be established in rodents considering the many differences that exist between rodents and humans. The domestic pig (Sus scrofa domesticus) has many anatomical, physiological, and immunological similarities to humans and has been widely used as a model for humans in biomedical and nutritional studies. Thus, the porcine model may be an alternative to rodent models in gut microbiota research. The current study was designed to evaluate the establishment of the same human donor microbiota in the rodent and pig models. Both germ-free piglets and mice (C3H/HeN) were transplanted with fecal microbiota from four human donors: Infant (0–5 m), child (1–12 yrs), adult (18–64 yrs), and elderly (65+ yrs). To monitor the establishment of the transplanted microbiota, weekly fecal samples were collected for 5 wks. All fecal samples were subjected to 16S rRNA gene-based amplicon sequencing using the Illumina MiSeqTM platform to characterize bacterial community composition. Unweighted unifrac distances were compared between the bacterial communities of the human donor and the corresponding HMA porcine and murine fecal samples. Statistical significance was tested using the Mann-Whitney U test (P = 0.05). This analysis suggested that more taxa are colonized in the mice compared to the piglets receiving the same infant donor microbiota, while for the child, adult, and elderly donors, the piglet model established the human donor microbiota better than the mice receiving the same donor samples. This suggests that in the latter stages of human development, more species of the human fecal inoculum colonizes the pig gut compared to the mouse gut.

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Comparison of the fecal microbiota of two free-ranging Chinese subspecies of the leopard (Panthera pardus) using high-throughput sequencing

PeerJ ◽

10.7717/peerj.6684 ◽

2019 ◽

Vol 7 ◽

pp. e6684 ◽

Cited By ~ 4

Author(s):

Siyu Han ◽

Yu Guan ◽

Hailong Dou ◽

Haitao Yang ◽

Meng Yao ◽

...

Keyword(s):

Bacterial Community ◽

Gut Microbiota ◽

High Throughput ◽

High Throughput Sequencing ◽

Bacterial Community Composition ◽

Rrna Gene ◽

Panthera Pardus ◽

Invasive Approach ◽

Fecal Samples ◽

Significant Difference

The analysis of gut microbiota using fecal samples provides a non-invasive approach to understand the complex interactions between host species and their intestinal bacterial community. However, information on gut microbiota for wild endangered carnivores is scarce. The goal of this study was to describe the gut microbiota of two leopard subspecies, the Amur leopard (Panthera pardus orientalis) and North Chinese leopard (Panthera pardus japonensis). Fecal samples from the Amur leopard (n = 8) and North Chinese leopard (n = 13) were collected in Northeast Tiger and Leopard National Park and Shanxi Tieqiaoshan Provincial Nature Reserve in China, respectively. The gut microbiota of leopards was analyzed via high-throughput sequencing of the V3–V4 region of bacterial 16S rRNA gene using the Life Ion S5™ XL platform. A total of 1,413,825 clean reads representing 4,203 operational taxonomic units (OTUs) were detected. For Amur leopard samples, Firmicutes (78.4%) was the dominant phylum, followed by Proteobacteria (9.6%) and Actinobacteria (7.6%). And for the North Chinese leopard, Firmicutes (68.6%), Actinobacteria (11.6%) and Fusobacteria (6.4%) were the most predominant phyla. Clostridiales was the most diverse bacterial order with 37.9% for Amur leopard and 45.7% for North Chinese leopard. Based on the beta-diversity analysis, no significant difference was found in the bacterial community composition between the Amur leopard and North Chinese leopard samples. The current study provides the initial data about the composition and structure of the gut microbiota for wild Amur leopards and North Chinese leopards, and has laid the foundation for further investigations of the health, dietary preferences and physiological regulation of leopards.

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Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Pathogens ◽

10.3390/pathogens10020149 ◽

2021 ◽

Vol 10 (2) ◽

pp. 149

Author(s):

Sreekumar Othumpangat ◽

William G. Lindsley ◽

Donald H. Beezhold ◽

Michael L. Kashon ◽

Carmen N. Burrell ◽

...

Keyword(s):

Healthy Volunteers ◽

Influenza A ◽

Influenza Infection ◽

Cell Types ◽

Airway Epithelial Cells ◽

Differentially Expressed ◽

Influenza B ◽

Airway Epithelial ◽

Monocyte Chemoattractant Protein 1 ◽

Novel Approach

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

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A Combined Analysis of Gut and Skin Microbiota in Infants with Food Allergy and Atopic Dermatitis: A Pilot Study

Nutrients ◽

10.3390/nu13051682 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1682

Author(s):

Ewa Łoś-Rycharska ◽

Marcin Gołębiewski ◽

Marcin Sikora ◽

Tomasz Grzybowski ◽

Marta Gorzkiewicz ◽

...

Keyword(s):

Atopic Dermatitis ◽

Food Allergy ◽

Gut Microbiota ◽

Bacterial Species ◽

Rrna Gene ◽

Healthy Children ◽

Skin Microbiota ◽

Fecal Samples ◽

Healthy Infants ◽

Α Diversity

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of Gemella among allergic infants, and Lactobacillus and Bacteroides among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host’s allergic state.

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Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

mSphere ◽

10.1128/msphere.00492-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 9

Author(s):

Alessandro Tanca ◽

Antonio Palomba ◽

Cristina Fraumene ◽

Valeria Manghina ◽

Michael Silverman ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Time Window ◽

High Resolution Mass Spectrometry ◽

Nod Mice ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Diabetic Mice ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice

ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.

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The Effect of White Rice and White Bread as Staple Foods on Gut Microbiota and Host Metabolism

Nutrients ◽

10.3390/nu10091323 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1323 ◽

Cited By ~ 2

Author(s):

Fumika Mano ◽

Kaori Ikeda ◽

Erina Joo ◽

Yoshihito Fujita ◽

Shunsuke Yamane ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Intervention ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

White Bread ◽

Fecal Samples ◽

White Rice ◽

Staple Foods ◽

Glucagon Like Peptide 1 ◽

Side Dishes

The purpose of this study was to examine the influence of two kinds of major Japanese staple foods, white rice and white bread, on gut microbiota against the background in which participants eat common side dishes. Seven healthy subjects completed the dietary intervention with two 1-week test periods with a 1-week wash-out period in cross-over design (UMIN registration UMIN000023142). White bread or white rice and 21 frozen prepared side dishes were consumed during the test periods. At baseline and at the end of each period, fasting blood samples, breath samples, and fecal samples were collected. For fecal samples, 16S rRNA gene sequencing was used to analyze the gut microbiota. After the bread period, the abundance of fecal Bifidobacterium genus (19.2 ± 14.5 vs. 6.2 ± 6.6 (%), p = 0.03), fasting glucagon-like peptide 1 (GLP-1) (13.6 ± 2.0 vs. 10.5 ± 2.9 (pg/mL), p = 0.03), and breath hydrogen (23.4 ± 9.9 vs. 8.2 ± 5.5 (ppm), p = 0.02) were significantly higher than those of after the rice period. Plasma SCFAs also tended to be higher after the bread period. White bread contains more dietary fiber than refined short grain rice. These findings suggest that indigestible carbohydrate intake from short grain rice as a staple food may be smaller than that of white bread.

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Evaluation of Influenza Patients Admitted in 2019–2020 Flu Season

Journal of Pediatric Infectious Diseases ◽

10.1055/s-0041-1741003 ◽

2022 ◽

Author(s):

Bahar Öztelcan Gündüz ◽

Erman Ataş ◽

Bülent Ünay ◽

Halit Halil

Keyword(s):

Physical Examination ◽

Chronic Diseases ◽

Influenza A ◽

Influenza Infection ◽

Febrile Seizures ◽

Influenza Viruses ◽

Influenza B ◽

Close Monitoring ◽

Group 2 ◽

Group 1

Abstract Objective Influenza viruses are among the most common respiratory pathogens for all age groups, and may cause seasonal outbreaks. The aim of our study was to describe the clinical characteristics of influenza cases in the 2019–2020 flu season and to study the risk factors for hospital admission and complications. Methods This was a retrospective study in 251 children (group 1: nonhospitalized; group 2: hospitalized) with influenza in the 2019–2020 flu season. Data on demographic features, influenza type, complaints, complications, and hospitalization length were collected and recorded. Results Influenza A was detected in 199 (79.3%) patients, and influenza B was detected in 52 (20.7%); 43.4% of patients were girls and 56.6% were boys. The mean age of the patients was 3.91 ± 3.3 years (16 days to 18 years). A total of 52 (20.7%) patients were hospitalized. The age of the patients in group 2 was lower than that in group 1 (3.1 vs. 4.2 years, p = 0.03). Group 2 patients were more likely to have creatine kinase (CK) elevation, febrile seizures, and physical examination abnormalities. Group 2 patients were also more likely to have influenza A. Patients with febrile seizures, chronic diseases, abnormal physical examination findings, developed complications, and additional drug use apart from oseltamivir in the treatment were also more likely to require hospitalization. Conclusion Infants and children with chronic diseases, history of febrile seizures, complications, and the use of drugs other than antiviral drugs should be carefully evaluated in case they need hospitalization. Increasing vaccination rates, initiation of antiviral treatment for selected patients, and close monitoring of patients in risk groups can decrease morbidity and mortality. Myalgias are a common complaint in patients with acute influenza infection. Previous studies suggest CK measurement be part of the work-up for the hospitalized patient with acute influenza infection.

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Probiotic Supplementation in a Clostridium difficile-Infected Gastrointestinal Model Is Associated with Restoring Metabolic Function of Microbiota

Microorganisms ◽

10.3390/microorganisms8010060 ◽

2019 ◽

Vol 8 (1) ◽

pp. 60

Author(s):

Mohd Baasir Gaisawat ◽

Chad W. MacPherson ◽

Julien Tremblay ◽

Amanda Piano ◽

Michèle M. Iskandar ◽

...

Keyword(s):

Gut Microbiota ◽

Alpha Diversity ◽

Gastrointestinal Disorder ◽

Short Chain Fatty Acids ◽

Rrna Gene ◽

Metabolic Function ◽

Microbial Composition ◽

Single Strain ◽

Fecal Samples ◽

Metabolic Functions

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.

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Deciphering the Bifidobacterial Populations within the Canine and Feline Gut Microbiota

Applied and Environmental Microbiology ◽

10.1128/aem.02875-19 ◽

2020 ◽

Vol 86 (7) ◽

Cited By ~ 4

Author(s):

Giulia Alessandri ◽

Christian Milani ◽

Leonardo Mancabelli ◽

Giulia Longhi ◽

Rosaria Anzalone ◽

...

Keyword(s):

Gut Microbiota ◽

Companion Animals ◽

Well Being ◽

Research Area ◽

Species Level ◽

Species Number ◽

Rrna Gene ◽

Social Relevance ◽

Fecal Samples ◽

Internally Transcribed Spacer

ABSTRACT During the course of evolution, dogs and cats have been subjected to extensive domestication, becoming the principal companion animals for humans. For this reason, their health care, including their intestinal microbiota, is considered of considerable importance. However, the canine and feline gut microbiota still represent a largely unexplored research area. In the present work, we profiled the microbiota of 23 feline fecal samples by 16S rRNA gene and bifidobacterial internally transcribed spacer (ITS) approaches and compared this information with previously reported data from 138 canine fecal samples. The obtained data allowed the reconstruction of the core gut microbiota of the above-mentioned samples coupled with their classification into distinct community state types at both genus and species levels, identifying Bacteroides, Fusobacterium, and Prevotella 9 as the main bacterial components of the canine and feline gut microbiota. At the species level, the intestinal bifidobacterial gut communities of dogs and cats differed in terms of both species number and composition, as emphasized by a covariance analysis. Together, our findings show that the intestinal populations of cats and dogs are similar in terms of genus-level taxonomical composition, while at the bifidobacterial species level, clear differences were observed, indicative of host-specific colonization behavior by particular bifidobacterial taxa. IMPORTANCE Currently, domesticated dogs and cats are the most cherished companion animals for humans, and concerns about their health and well-being are therefore important. In this context, the gut microbiota plays a crucial role in maintaining and promoting host health. However, despite the social relevance of domesticated dogs and cats, their intestinal microbial communities are still far from being completely understood. In this study, the taxonomical composition of canine and feline gut microbiota was explored at genus and bifidobacterial species levels, allowing classification of these microbial populations into distinct gut community state types at either of the two investigated taxonomic levels. Furthermore, the reconstruction of core gut microbiota coupled with covariance network analysis based on bifidobacterial internally transcribed spacer (ITS) profiling revealed differences in the bifidobacterial compositions of canine and feline gut microbiota, suggesting that particular bifidobacterial species have developed a selective ability to colonize a specific host.

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Identification and Characterization of Novel Compounds with Broad-Spectrum Antiviral Activity against Influenza A and B Viruses

Journal of Virology ◽

10.1128/jvi.02149-19 ◽

2020 ◽

Vol 94 (7) ◽

Cited By ~ 6

Author(s):

Jun-Gyu Park ◽

Ginés Ávila-Pérez ◽

Aitor Nogales ◽

Pilar Blanco-Lobo ◽

Juan C. de la Torre ◽

...

Keyword(s):

Antiviral Activity ◽

Rna Polymerase Ii ◽

Broad Spectrum ◽

Influenza A ◽

Viral Infections ◽

Influenza Infection ◽

Inhibitory Effect ◽

Influenza Viruses ◽

Influenza B ◽

Genome Replication

ABSTRACT Influenza A (IAV) and influenza B (IBV) viruses are highly contagious pathogens that cause fatal respiratory disease every year, with high economic impact. In addition, IAV can cause pandemic infections with great consequences when new viruses are introduced into humans. In this study, we evaluated 10 previously described compounds with antiviral activity against mammarenaviruses for their ability to inhibit IAV infection using our recently described bireporter influenza A/Puerto Rico/8/34 (PR8) H1N1 (BIRFLU). Among the 10 tested compounds, eight (antimycin A [AmA], brequinar [BRQ], 6-azauridine, azaribine, pyrazofurin [PF], AVN-944, mycophenolate mofetil [MMF], and mycophenolic acid [MPA]), but not obatoclax or Osu-03012, showed potent anti-influenza virus activity under posttreatment conditions [median 50% effective concentration (EC50) = 3.80 nM to 1.73 μM; selective index SI for 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, >28.90 to 13,157.89]. AmA, 6-azauridine, azaribine, and PF also showed potent inhibitory effect in pretreatment (EC50 = 0.14 μM to 0.55 μM; SI-MTT = 70.12 to >357.14) or cotreatment (EC50 = 34.69 nM to 7.52 μM; SI-MTT = 5.24 to > 1,441.33) settings. All of the compounds tested inhibited viral genome replication and gene transcription, and none of them affected host cellular RNA polymerase II activities. The antiviral activity of the eight identified compounds against BIRFLU was further confirmed with seasonal IAVs (A/California/04/2009 H1N1 and A/Wyoming/3/2003 H3N2) and an IBV (B/Brisbane/60/2008, Victoria lineage), demonstrating their broad-spectrum prophylactic and therapeutic activity against currently circulating influenza viruses in humans. Together, our results identified a new set of antiviral compounds for the potential treatment of influenza viral infections. IMPORTANCE Influenza viruses are highly contagious pathogens and are a major threat to human health. Vaccination remains the most effective tool to protect humans against influenza infection. However, vaccination does not always guarantee complete protection against drifted or, more noticeably, shifted influenza viruses. Although U.S. Food and Drug Administration (FDA) drugs are approved for the treatment of influenza infections, influenza viruses resistant to current FDA antivirals have been reported and continue to emerge. Therefore, there is an urgent need to find novel antivirals for the treatment of influenza viral infections in humans, a search that could be expedited by repurposing currently approved drugs. In this study, we assessed the influenza antiviral activity of 10 compounds previously shown to inhibit mammarenavirus infection. Among them, eight drugs showed antiviral activities, providing a new battery of drugs that could be used for the treatment of influenza infections.

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