Age and injury size influence the magnitude of fecal dysbiosis in adult burn patients

Author(s):  
Kiran Dyamenahalli ◽  
Kevin Choy ◽  
Daniel N Frank ◽  
Kevin Najarro ◽  
Devin Boe ◽  
...  

Abstract Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 were stratified based on age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = 0.014) in overall microbiota community composition (i.e., beta diversity) were measured across the four patient groups, young <10% TBSA, young ≥10% TBSA, older <10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = 0.013) and trended with age (P = 0.087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = 0.0023) and Shannon diversity (P = 0.0033) between the groups. There were significant correlations between individual bacterial species and levels of SCFA. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsen clinical outcomes with heightened morbidity and mortality.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 744-744
Author(s):  
Sonal Suresh Noticewala ◽  
Daniel Lin ◽  
Ramez Kouzy ◽  
Anirban Maitra ◽  
Lauren Elizabeth Colbert ◽  
...  

744 Background: While most studies evaluating the microbiome in gastrointestinal cancers analyze stool, little is known about the microbiota of the peri-tumoral and intra-tumoral environment. Here, we evaluated the intra-tumoral and peri-tumoral (duodenum and normal pancreas) microbiome for paired duodenal, normal pancreas and resected tumor specimens from pancreatic cancer patients. The purpose of this study was to describe the similarities and differences within patient microbiota. Methods: Fifteen specimens from 5 patients with pancreatic cancer were collected during surgical resection. Genomic bacterial DNA was extracted from these specimens and underwent 16S rRNA sequencing. Alpha (Inverse Simpson) and beta diversity were calculated, and relative abundances of individual bacterial species were compared. Sorensen distance was used the evaluate the spread in beta diversity between paired sample types. Results: Of the five patients who underwent resection, the following baseline characteristics were obtained: median age = 65 years (range 55 -80 years), 2/5 patients were treated with gemcitabine/abraxane, 3/5 patients were treated with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX); 4/5 patients received pre-operative radiation. 16s sequencing analysis of the pancreatic tumor showed the dominant genus to be Escherichia/Shigella (10.6%). Bradyrhizobium (10.1 %) was dominant in the normal pancreas . Escherichia/Shigella (14.3%) was abundant in the duodenum. There was a trend towards higher alpha diversity in tumor vs. normal duodenum/ pancreas (p = 0.12). Sorensen distance was statistically different between sample types (p = 0.004), with duodenal samples most consistent (distance = 67.82), and tumor vs. normal pancreas (81.86) and tumor vs. other tumor samples the most heterogeneous (78.5). Conclusions: This pilot data suggests that the pancreatic tumor microbiome is distinct from the normal pancreas and duodenal microbiome, which indicates tumor specific bacteria should be studied. In future studies, intra-tumoral microbiome may be more relevant to associations with outcomes and treatment response than stool or intestinal microbiome studies.


Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 463
Author(s):  
Mariusz Sikora ◽  
Albert Stec ◽  
Magdalena Chrabaszcz ◽  
Aleksandra Knot ◽  
Anna Waskiel-Burnat ◽  
...  

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Melissa H. Althouse ◽  
Christopher Stewart ◽  
Weiwu Jiang ◽  
Bhagavatula Moorthy ◽  
Krithika Lingappan

Abstract Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 203-203
Author(s):  
Huyen Tran ◽  
Timothy J Johnson

Abstract The objective of this study was to evaluate effects of feeding two phytogenic products (PHY1 and PHY2; blends of essential oils and plant extracts) in diets with or without antibiotics (AureoMix S 10-10; AB) on fecal microbiome of nursery pigs. A total of 400 nursery pigs (6.8 kg BW; 20 d of age) were fed one of the six dietary treatments (9 pens/treatment), including: control (0% AB; 0% phytogenics), 0.5% AB, phytogenics (0.02% PHY1 or 0.03% PHY2) or the combination of phytogenic and AB (PHY1 x AB or PHY2 x AB). On d 46 postweaning, 48 fecal samples were collected (1 pig/pen; 7–9 pigs/treatment) and were subjected to the analyses of microbial communities by using 16S rRNA V4 amplicon sequencing with Illumina MiSeq. The sequence data were analyzed by using Qiime and the rarefied OTU table was submitted to Calypso to evaluate the alpha and beta diversity, taxonomic classification, and the differential taxa associated to the dietary treatments. There were differences among treatments on alpha diversity, where the control and PHY2 pigs had lower OTU richness (P = 0.05) and chao1 index (P < 0.10) compared to pigs fed AB alone or AB with phytogenics. There were also differences among treatments on microbial beta diversity of pigs (P < 0.01). The most abundant phyla included Firmicute, Bacteroidetes, Actinobacteria, Tenericutes, Proteobacteria, Spirochaetes, and TM7. At family level, pigs fed AB had greater Ruminococcaceae compared to the control, but lower Coriobacteriaceae and Erysipelotrichaceae compared to PHY1 or PHY2 group (P < 0.05). Feature selection by LEfSe indicated that dominant genus associated to AB treatment was Unclassified RF39, while dominant genera associated to PHY2 treatment were Cantenibacterium, unclassified Coriobacteriaceae, Blautia, Eubacterium, and Collinsella. In conclusion, feeding AB and phytogenic products had different impacts on the fecal bacteria of nursery pigs.


2021 ◽  
Author(s):  
Diana J. Zajac ◽  
Stefan J. Green ◽  
Lance A. Johnson ◽  
Steven Estus

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.


2015 ◽  
Vol 12 (12) ◽  
pp. 70-76 ◽  
Author(s):  
S Rajbahak ◽  
C Shrestha ◽  
A Singh

A prospective study was carried out in 42 burn patients admitted in burn unit of Bir Hospital over a period of six months from September 2011 to February 2012 to evaluate time-related changes in aerobic bacterial colonization and their susceptibility pattern. Periodic swabs were taken from the burn wound on 1st, 2nd, 3rd and 4th weeks to see the changing pattern of organisms during hospital stay of patients. Wound swabs obtained from the burn patients were subjected to microbiological analysis. The isolates were identified by standard microbiological techniques and their antibiotic susceptibility was determined by using Kirby-Bauer disk diffusion techniques. In the present study burn injury was highest in the age group 25-34 years (28.6%). Male to female ratio was 1:1.5. Fire was the major cause of burn (78.6%) followed by scald burn (7.1%). Among the 168 samples, single organism was isolated in 47.6% samples and mixed organisms in 39.9% and no growth in 12.5%. A total of 215 bacterial species were isolated from 168 samples in which Pseudomonas aeruginosa accounted for the highest percentage 45.6% followed by Staphylococcus aureus (19.1%), Acinetobacter spp. (17.7%) and coagulase negative Staphylococci (CONS) (5.6%). Gram negative bacteria were the dominating bacteria all over the study period and exhibited lower sensitivity to most of the antibiotic used. Furthermore, P. aeruginosa was least sensitive to most antibiotics used. Amikacin was the drug of choice for most Gram negative bacteria and vancomycin was found to be susceptible drug for Gram positive organisms (S. aureus and CONS). Continuous survey and analysis of changing microbial flora and their antibiogram in burn patients help in timely detection and control of spread of infection and also help to review effective antibiotic policies.Scientific World, Vol. 12, No. 12, September 2014, page 70-76      


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262108
Author(s):  
Mohammad El Mouzan ◽  
Asaad Assiri ◽  
Ahmed Al Sarkhy ◽  
Mona Alasmi ◽  
Anjum Saeed ◽  
...  

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.


2020 ◽  
Author(s):  
Kendra E. Walters ◽  
Jennifer B.H. Martiny

AbstractBacteria are essential parts of ecosystems and are the most abundant organisms on the planet. Yet, we still do not know which habitats support the highest diversity of bacteria across multiple scales. We analyzed alpha-, beta-, and gamma-diversity of bacterial assemblages using 11,680 samples compiled by the Earth Microbiome Project. We found that soils contained the highest bacterial richness within a single sample (alpha-diversity), but sediment assemblages were the most diverse at a global scale (gamma-diversity). Sediment, biofilms/mats, and inland water exhibited the most variation in community composition among geographic locations (beta-diversity). Within soils, agricultural lands, hot deserts, grasslands, and shrublands contained the highest richness, while forests, cold deserts, and tundra biomes consistently harbored fewer bacterial species. Surprisingly, agricultural soils encompassed similar levels of beta-diversity as other soil biomes. These patterns were robust to the alpha- and beta-diversity metrics used and the taxonomic binning approach. Overall, the results support the idea that spatial environmental heterogeneity is an important driver of bacterial diversity.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S594-S595
Author(s):  
S Ellul ◽  
P Rausch ◽  
A Pisani ◽  
C Bang ◽  
P Ellul ◽  
...  

Abstract Background The role of microbiome with the alteration between commensal and pathogenic bacteria, has been linked to IBD. Meanwhile Escherichia coli Nissle 1917, Lactobacillus rhamnosus GG (LGG) and faecal transplantation are used in IBD. The aim of this study was to prospectively determine faecal microbiota composition of newly diagnosed treatment naïve IBD patients. Methods Patients diagnosed with IBD between January 2018-September 2019 were recruited. Clinical data was collected and patients asked to submit stool samples for microbiome analysis. Stool samples from a control population were recruited and analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq. Results 100 IBD patients (CD: n=46, UC: n=53 & IBDU: n=1) and 97 controls with specific inclusion and exclusion criteria collected. IBD patients were noted to display reduced average species richness and community evenness compared to healthy controls (Alpha- Diversity) (Figure 1). Beta-diversity between microbial communities of healthy individuals and IBD patients was significantly different, but no observed separation between the two types of IBD was noted (Figure 2). 11 ASVs were abundant in CD patients including: ASV-70 – Lactobacillus gasseri, Klebsiella uncl., Candidatus-saccharibacteria, ASV-157 - Acteroides clarus and ASV 249- Parasutterella uncl. In UC cohort, 10 ASVs were abundant including: ASV 6-Escherichia/Shigella uncl., ASB-41-Sutterella wadsworthensis, ASV 44- Bacteroides faecis and Actinobacteria. An association between UC and ASV 313 (Faecalibacteria) was present. In the microbiome of healthy controls, 20 ASVs were abundant, including: ASV-14 G-Alistipes uncl., ASV 20-(Akkermansia muciniphila),(bacterium belonging to the phylum Verrucomicrobia), ASV 321 (Clostridia uncl.), ASV 96 (Rumminococcaceae uncl.), Alistepes uncl. (ASV 61), Subdoligranulum uncl. (ASV 453) and the unclassifiable bacteria. A higher amount of Verrucomicrobia was present in the healthy group as opposed to the IBD. Conclusion ASV 249- Parasutterella unlc., was indicative of CD associated microbiome through the indicator species analysis. Typical microbiome changes in IBD patients include increased abundance of the pro-inflammatory species with a reduction in anti-inflammatory bacterial species, with a noticeable reduction in alpha and beta diversity. In the local cohort, a particular change in the local α- and β diversity was noted to be present between healthy controls and IBD cohort. This could be a potential way in which targeted therapeutic approaches using specific dosage and durations of probiotic or faecal transplant can be used to alter faecal microbiome using specific bacteria present in healthy controls and with elimination of potentially harmful bacteria in IBD patients. Figure 1: Alpha diversity between different Groups using Chao1 species richness and Simpson 1-D Figure 2: Beta diversity between different groups using Bray-Curtis dissimilarity, Jaccard distance.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marie van der Merwe ◽  
Sunita Sharma ◽  
Jade Caldwell ◽  
Nicholas Smith ◽  
Richard Bloomer ◽  
...  

Abstract Objectives Time-restricted feeding strategies have been shown to normalize obesity parameters, even under high fat feeding conditions. The objective of this study is to examine whether timed feeding alters parameters of gut health or intestinal microbiome composition. Methods C57BL/6 male mice were randomized to Chow or a high fat diet (HFD) for 6 weeks, followed by a switch from HFD to 1) Chow (sChow), 2) Purified Vegan – Daniel Fast (DF), 3) HFD ad lib, 4) HFD time restricted (TRF), 5) HFD alternative day fasting (ADF), or 6) HFD 60% caloric restriction (CR) for an additional 8 weeks. Results We observed that body mass gain was reduced for all intervention groups (P ≤ 0.0001). Small intestinal length and cecal weight were increased in Chow, sChow and DF (P ≤ 0.02), while total cecal short chain fatty acid (SCFA) concentration was non-significantly increased for all groups consuming the HFD. Proprionate was specifically increased in the Chow, sChow and DF groups (P ≤ 0.02). Chow fed microbiota remained stable in taxonomic composition and alpha diversity (Shannon diversity index) throughout the study. HF fed microbiota displayed lower alpha diversity along with reduced phylum levels of Bacteroidetes and increase Firmicutes. Animals switched from HF to Chow demonstrated a rapid transition in taxonomic composition, alpha, and beta diversity that initially resembled HF, but clustered closely with Chow by weeks 4 and 8 of intervention. After 8 weeks on the respective dietary protocols, alpha diversity of the DF was most similar to Chow fed animals and also resulted in the largest increase in Bacteriodetes and largest decrease in Firmicutes. Beta diversity (weighted UniFrac) showed Chow, sChow, and DF clustered together, while high fat fed groups (HF, CR, ADF, and TRF) clustered. Compared with HF controls, CR and TRF led to a relative increase in the classes Clostridia, Deferribacteres and Deltaproteobacteria. The taxonomic composition and alpha diversity of ADF fasting resembled HF under fed conditions, while ADF under fasting conditions more closely resembled CR and TRF. Conclusions In conclusion, timed feeding on a high fat diet did not result in significant changes in the microbiome, demonstrating that diet, and not fasting is the major determinant for microbiome composition. Funding Sources University of Memphis & Children's Foundation Research Institute, Memphis.


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