scholarly journals Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation

mSystems ◽  
2021 ◽  
Author(s):  
Evgenii I. Olekhnovich ◽  
Artem B. Ivanov ◽  
Vladimir I. Ulyantsev ◽  
Elena N. Ilina

We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S625-S625
Author(s):  
Peter J Larson ◽  
Julia Oh ◽  
Julie Robison ◽  
James Grady ◽  
George Kuchel

Abstract Background Despite their elevated risk for morbidity and mortality from infections, the microbiota of older adults remain understudied. While colonization resistance from resident microflora is a promising means to prevent infections, little is known about pathogenicity reservoirs and colonization resistance in this vulnerable population. Here we study the skin, oral, and gut microbiome dynamics of older adults in both community and Skilled Nursing Facility (SNF) settings, investigating relationships between age, frailty, environment, microbiota, and pathogenicity reservoirs. Methods We conducted a longitudinal metagenome survey of 47 adults age 65+ years of age; 22 residents of 3 different SNFs and 25 community dwelling individuals. We performed metagenomic whole genome shotgun sequencing on stool, oral, and skin samples from 8 sites, 1421 total. To correlate clinical and behavioral variables, we measured frailty, collected medical records, and interviewed participants on diet and lifestyle. We also draw comparisons with previous younger cohorts. Results • Compared to younger adults, the skin microbiota of older adults was characterized by ◦ High heterogeneity ◦ Decreased stability over time, suggesting increased susceptibility to colonization and pathogenicity ◦ Compositional differences including significantly lower levels of Cutibacterium acnes, with reciprocal increases in Staphylococci, Corynebacteria, and Malassezia • In older adults, Frailty (Rockwood) was found to have linear correlation with relative abundance of species relevant to infection risk including acnes, staphylococci, streptococci, E. coli, Akkermansia mucinophila, and Enterococcus faecalis. • The skin, oral, and gut microbiota of SNF residents had substantially elevated virulence factor and antibiotic resistance genes. Conclusion To the best of our knowledge, this is largest report to date of the skin metagenome in older adults. We demonstrate distinct and significant differences between cohorts with clinically relevant implications. We believe these results may inform infection control and prevention by increasing our understanding of colonization resistance and pathogenicity reservoirs, as well as advance our knowledge of the relationship between aging, the microbiome, and infections. Disclosures All Authors: No reported disclosures


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yu Li ◽  
Zeling Xu ◽  
Wenkai Han ◽  
Huiluo Cao ◽  
Ramzan Umarov ◽  
...  

Abstract Background The spread of antibiotic resistance has become one of the most urgent threats to global health, which is estimated to cause 700,000 deaths each year globally. Its surrogates, antibiotic resistance genes (ARGs), are highly transmittable between food, water, animal, and human to mitigate the efficacy of antibiotics. Accurately identifying ARGs is thus an indispensable step to understanding the ecology, and transmission of ARGs between environmental and human-associated reservoirs. Unfortunately, the previous computational methods for identifying ARGs are mostly based on sequence alignment, which cannot identify novel ARGs, and their applications are limited by currently incomplete knowledge about ARGs. Results Here, we propose an end-to-end Hierarchical Multi-task Deep learning framework for ARG annotation (HMD-ARG). Taking raw sequence encoding as input, HMD-ARG can identify, without querying against existing sequence databases, multiple ARG properties simultaneously, including if the input protein sequence is an ARG, and if so, what antibiotic family it is resistant to, what resistant mechanism the ARG takes, and if the ARG is an intrinsic one or acquired one. In addition, if the predicted antibiotic family is beta-lactamase, HMD-ARG further predicts the subclass of beta-lactamase that the ARG is resistant to. Comprehensive experiments, including cross-fold validation, third-party dataset validation in human gut microbiota, wet-experimental functional validation, and structural investigation of predicted conserved sites, demonstrate not only the superior performance of our method over the state-of-art methods, but also the effectiveness and robustness of the proposed method. Conclusions We propose a hierarchical multi-task method, HMD-ARG, which is based on deep learning and can provide detailed annotations of ARGs from three important aspects: resistant antibiotic class, resistant mechanism, and gene mobility. We believe that HMD-ARG can serve as a powerful tool to identify antibiotic resistance genes and, therefore mitigate their global threat. Our method and the constructed database are available at http://www.cbrc.kaust.edu.sa/HMDARG/.


Author(s):  
Gabriela Reichert ◽  
Stephan Hilgert ◽  
Johannes Alexander ◽  
Júlio César Rodrigues de Azevedo ◽  
Tobias Morck ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Sun ◽  
Xiangzhu Zhu ◽  
Xiang Huang ◽  
Harvey J. Murff ◽  
Reid M. Ness ◽  
...  

AbstractThe gut microbiota plays an important role in human health and disease. Stool, rectal swab and rectal mucosal tissue samples have been used in individual studies to survey the microbial community but the consequences of using these different sample types are not completely understood. In this study, we report differences in stool, rectal swab and rectal mucosal tissue microbial communities with shotgun metagenome sequencing of 1397 stool, swab and mucosal tissue samples from 240 participants. The taxonomic composition of stool and swab samples was distinct, but less different to each other than mucosal tissue samples. Functional profile differences between stool and swab samples are smaller, but mucosal tissue samples remained distinct from the other two types. When the taxonomic and functional profiles were used for inference in association with host phenotypes of age, sex, body mass index (BMI), antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) use, hypothesis testing using either stool or rectal swab gave broadly significantly correlated results, but inference performed on mucosal tissue samples gave results that were generally less consistent with either stool or swab. Our study represents an important resource for determination of how inference can change for taxa and pathways depending on the choice of where to sample within the human gut.


2020 ◽  
Author(s):  
Pratikshya Ray ◽  
Debasmita Das ◽  
Uday Pandey ◽  
Palok Aich

AbstractThe gut is the largest reservoir of the resident microbiota. The microbiota can affect the host behavior and immunity. While the consequence of treatment with antibiotics on the gut microbiota can be destructive but can be utilized as a tool to understand the host immunity and behavior. The magnitude of perturbation and time needed for the restoration of gut microbiota can depend on the immune bias of the host. In the current study, we therefore, observed the perturbation and restoration kinetics of gut microbiota following treatment with vancomycin and its effect on the host physiology in both Th1-(C57BL/6) and Th2-(BALB/c) biased mice. A comparative metagenomic analysis revealed that the treatment with vancomycin caused a significant decrease in the abundance of Firmicutes and Bacteroidetes phyla and an initial increase in Proteobacteria. Increase in Proteobacteria decreased with continued treatment with vancomycin to result into a significant rise in Verrucomicrobia phylum. We established the patterns of gut microbiota alteration and its effect on a) the behavior of mice, b) expression of key brain molecules and b) immunity related genes. We followed the gut microbiome restoration for a period of two months following withdrawal of treatment with vancomycin. Maximum restoration (>70%) of gut microbiota happened by the 15th day of withdrawal. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. The results, in general, revealed that along with the restoration of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal level.


Author(s):  
Antonella Gagliardi ◽  
Valentina Totino ◽  
Fatima Cacciotti ◽  
Valerio Iebba ◽  
Bruna Neroni ◽  
...  

A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.


2018 ◽  
Vol 62 (5) ◽  
Author(s):  
N. J. Ajami ◽  
J. L. Cope ◽  
M. C. Wong ◽  
J. F. Petrosino ◽  
L. Chesnel

ABSTRACT Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates a reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time. Mice were exposed to fidaxomicin or vancomycin by oral gavage for 3 days and subsequently challenged with C. difficile spores at predetermined time points up to 21 days postexposure to antibiotics. Fecal samples were subsequently collected for analysis. Twenty-four hours postchallenge, mice were euthanized and the colon contents harvested. The microbiota was characterized using 16S rRNA gene sequencing. All fidaxomicin-exposed mice (except for one at day 8) were resistant to C. difficile colonization. However, 9 of 15 vancomycin-exposed mice were susceptible to C. difficile colonization until day 12. All vancomycin-exposed mice recovered colonization resistance by day 16. Bacterial diversity was similar prior to antibiotic exposure in both arms and decreased substantially after exposure. A shift in taxonomic structure and composition occurred after both exposures; however, the shift was greater in vancomycin-exposed than in fidaxomicin-exposed mice. In summary, compared with vancomycin, fidaxomicin exposure had less impact on microbiota composition, promoted faster microbial recovery, and had less impact on the loss of C. difficile colonization resistance.


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