Biology subjects

Shetty, S. A.

Publications and source records attributed to Shetty, S. A..

7 recordsLinked to original sources

bioRxiv2024

A three-country analysis of the gut microbiome indicates taxon associations with diet vary by location and strain

Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. While significant efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research lacks representation from low- and middle-income countries such as Mexico. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,291 individuals across three countries, we examine two bacterial genera prevalent in the human gut, Prevotella and Faecalibacterium, which have gained significant attention due to their potential roles in human health. We find that they show significant associations with many aspects of diet, but that these associations vary in scale and direction, depending on the level of metagenomic resolution and the contextual population. These results highlight the growing importance of assembling metagenomic datasets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.

microbiology↗

bioRxiv2023

Frailty is related to serum inflammageing markers: results from the VITAL study

Frailty describes an age-associated state in individuals with an increased vulnerability and less resilience against adverse outcomes. To score frailty, studies have employed the questionnaires, such as the SF-36 and EQ-5D-3L, or the Frailty Index, a composite score based on deficit accumulation. Furthermore, ageing of the immune system is often accompanied by a state of low-grade inflammation (inflammageing). Here, we aimed to associate 29 circulating markers of inflammageing with frailty measures in a prospective cohort study to understand the mechanisms underlying ageing. Frailty measures and inflammageing markers were assessed in 317 participants aged 25-90. We determined four different measures of frailty: the Frailty Index based on 31 deficits, the EQ-5D-3L and two physical domains of the SF-36. Serum/plasma levels of inflammageing markers and CMV/EBV seropositivity were measured using different techniques: Quanterix, Luminex or ELISA. All four measures of frailty strongly correlated with age and BMI. Nineteen biomarkers correlated with age, some in a linear fashion (IL-6, YKL-40), some only in the oldest age brackets (CRP), and some increased at younger ages and then plateaued (CCL2, sIL-6R). After correcting for age, biomarkers, such as IL-6, CRP, IL-1RA, YKL-40 and elastase, were associated with frailty. When corrected for BMI, the number of associations reduced further. In conclusion, inflammageing markers, particularly markers reflecting innate immune activation, are related to frailty. These findings indicate that health decline and the accumulation of deficits with age is accompanied with a low-grade inflammation which can be detected by specific inflammatory markers.

immunology↗

bioRxiv2022

Standardization of laboratory practices for the study of the human gut microbiome

Technical advances in next-generation sequencing (NGS) have made it more accessible to study the human microbiome, resulting in more available data and knowledge. As a result of this expansion of data, the need to obtain comparable and reproducible data has become one of the most important challenges facing microbiome research nowadays. In this study, we aim to contribute to existing knowledge to promote high quality microbiome data and minimize bias introduced by technical variation throughout studies, from sample collection, storage, to sequencing strategies. While immediate freezing upon sampling has been the "golden standard" in the field, this method is often logistically difficult and expensive, becoming a limiting factor when conducting large scale studies or in regions where maintenance of the cold-chain presents difficulties. Therefore, we compared the immediately frozen method to storage at room temperature for 3 - 5 days in two commercially available stabilization solutions (Omnigene gut and Zymo Research) as well as without buffer. Other important aspects were tested, such as DNA extraction, bacterial DNA input or number of PCR cycles. Method choice for cell disruption resulted in the biggest difference in compositional profiles. The changes observed in microbiome profiles in samples stored at RT without stabilization solution was prevented by the use of these. For library preparation and sequencing, we found the highest heterogeneity in the DNA extraction step, followed by the use of different Illumina barcodes, indicating that both of these steps have an impact during library preparation. We did not observe a batch effect between the different sequencing runs. Standardized methods are important to allow comparison of results between different research groups worldwide and reliably expand microbiome data to a broad range of diseases, ethnical backgrounds and geographic locations. A more global perspective will increase our understanding of the human microbiome around the world.

systems biology↗

bioRxiv2021

Associations and recovery dynamics of the nasopharyngeal microbiota during influenza-like illness in the aging population

BackgroundOlder adults are more susceptible to respiratory pathogens, several of which have been associated with an altered respiratory microbiota. Influenza-like illness (ILI), a disease caused by respiratory pathogens including but not exclusively by influenza virus, is a major health concern in this population. However, there is little information on changes in the nasopharyngeal (NP) microbiota of older adults associated with respiratory infections identified by/ reported as ILI, as well as its dynamics during recovery. Here, we compared the NP microbiota in older adults who presented with ILI (n= 240) to the NP microbiota in older adults not reporting an ILI event (n= 157) during the 2014-2015 influenza season. To investigate the dynamics of the microbiota from the acute phase to the recovery phase of the infection, participants reporting an ILI event were sampled at onset of infection (<72 hours), at 14 days and at 7-9 weeks after infection (recovery sample). ResultsCross-sectional analysis of the microbiota at the different time-points showed no differences in alpha diversity between the groups. A small but significant effect of the ILI was observed on the microbiota community and structure when compared to controls and recovery samples. Furthermore, the NP microbiota exhibited inter-individual differences in dynamics from onset of ILI to recovery. Corynebacterium, one of the keystone species in the upper respiratory tract, was negatively associated with ILI and its abundance increased after recovery. Potential pathobionts such as Haemophilus, Porphyromonas and Gemella had higher abundances during acute-ILI. Stability and changes in the NP microbial community showed individual dynamics. Key core genera, Corynebacterium, Moraxella and Dolosigranulum exhibited higher inter-individual variability in acute-ILI, but showed comparable variability to controls after recovery. Participants in the ILI group with higher core microbiota abundances at the acute phase showed higher microbiota stability after recovery. ConclusionsOur findings demonstrate that acute-ILI is associated with small but significant alterations in the phylogenetic structure of the NP microbiota in older adults. The observed variation in the core microbiota suggests potential imbalances in the ecosystem, which could play a role in the recovery of the NP microbiota after an ILI event.

microbiology↗

bioRxiv2020

Unravelling lactate-acetate conversion to butyrate by intestinal Anaerobutyricum and Anaerostipes species

The D-and L-forms of lactate are important fermentation metabolites produced by intestinal bacteria but have been found to negatively affect mucosal barrier function and human health. Of interest, both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, including Anaerobutyricum and Anaerostipes spp. This is a low energy yielding process with a partially unknown pathway in Anaerobutyricum and Anaerostipes spp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We focused on Anaerobutyricum soehngenii and compared its growth on lactate with that on sucrose and sorbitol. Comparative proteomics revealed a unique active gene cluster that was abundantly expressed when grown on lactate. This active gene cluster, lctABCDEF, encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), along with a nickel-dependent racemase (lctE) and a lactate permease (lctF). Extensive search of available genomes of intestinal bacteria revealed this gene cluster to be highly conserved in only Anaerobutyricum and Anaerostipes spp. The present study demonstrates that A. soehngenii and several related Anaerobutyricum and Anaerostipes spp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.

microbiology↗

bioRxiv2019

Metagenomic- and cultivation-based exploration of anaerobic chloroform biotransformation in hypersaline sediments as natural source of chloromethanes

Chloroform (CF) is an environmental contaminant that can be naturally formed in various environments ranging from forest soils to salt lakes. Here we investigated CF removal potential in sediments obtained from hypersaline lakes in Western Australia. Reductive dechlorination of CF to dichloromethane (DCM) was observed in enrichment cultures derived from sediments of Lake Strawbridge, which has been reported as a natural source of CF. The lack of CF removal in the abiotic control cultures without artificial electron donors indicated that the observed CF removal is a biotic process. Metabolite analysis with 13C labelled CF in the sediment-free enrichment cultures (pH 8.5, salinity 5%) revealed that increasing the vitamin B12 concentration from 0.04 to 4 M enhanced CF removal, reduced DCM formation, and increased 13CO2 production, which is likely a product of CF oxidation. Known organohalide-respiring bacteria and reductive dehalogenase genes were neither detected by quantitative PCR nor metagenomic analysis. Rather, members of the order Clostridiales, known to co-metabolically transform CF to DCM and CO2, were detected in the enrichment cultures. Genome-resolved metagenome analysis indicated that their genomes encode enzymatic repertoires for the Wood-Ljungdahl pathway and cobalamin biosynthesis that are known to be involved in co-metabolic CF transformation. ImportanceMore than 90% of the global CF emission to the atmosphere originates from natural sources, including saline environments such as salt lake sediments. However, knowledge about the microbial metabolism of CF in such extreme environments is lacking. Here we showed CF transformation potential in a hypersaline lake that was reported as a natural source of CF production. Application of interdisciplinary approaches of microbial cultivation, stable isotope labelling, and metagenomics aided in defining potential chloroform transformation pathways. This study indicates that microbiota may act as a filter to reduce CF emission from hypersaline lakes to the atmosphere, and expands our knowledge of halogen cycling in extreme hypersaline environments.

microbiology↗

bioRxiv2017

Comparison of Small Gut and Whole Gut Microbiota of First-Degree Relatives with Adult Patients with Celiac Disease and Controls

Recent studies on celiac disease (CeD) have shown the role of gut microbiota alterations in CeD pathogenesis. Whether this alteration in the microbial community is the cause or effect of the disease is not well understood, especially in adult onset of disease. The first-degree relatives (FDRs) of CeD patients may provide an opportunity to study gut microbiome in pre-disease state as FDRs are genetically susceptible to CeD. By using 16S rRNA gene sequencing, we observed between the disease condition (CeD), pre-disease (FDR) and control subjects. However, differences were observed at the level of amplicon sequence variant (ASV), suggesting alterations in specific taxa between pre-diseases and diseased condition. Duodenal biopsies showed higher differences in ASVs compared to faecal samples indicating larger disruption of microbiota at disease site. Increased abundance of specific Helicobacter ASVs were observed in duodenum of CeD when compared to FDR (p < 0.01). In case of fecal samples CeD microbiome and Actinomyces. In addition, predicted functional metagenome showed reduced ability of gluten that ecosystem level diversity measures (except in the duodenum) were not significantly different is characterized by reduced abundance of beneficial taxa such as Akkermansia, Ruminococcus degradation by CeD faecal microbiota in comparison to FDRs and controls.

microbiology↗