Biology subjects

Rohr, C.

Publications and source records attributed to Rohr, C..

6 recordsLinked to original sources

bioRxiv2025

Using low pass whole metagenome sequencing for gut microbiome profiling in an Argentine urban population

Modern urban diets are linked to gut microbiome dysbiosis and increased risk of chronic disease. While 16S rRNA sequencing is widely used, low-pass whole metagenome sequencing (WMS) offers superior insight into microbial functional capacity and community structures. In this study, we utilized low-pass WMS to characterize the gut microbiome of an Argentine urban population. We compared a health-screened Reference cohort (n=94) with an unscreened Average urban cohort (n=527), for which we analyzed taxonomic structure, microbial diversity, and predicted metabolic potential. The Average cohort displayed significantly lower alpha-diversity, primarily driven by reduced community evenness rather than richness. Functionally, this cohort showed a significantly diminished predicted capacity for synthesizing beneficial short-chain fatty acids (SCFAs) and essential vitamins B9 and B12. A longitudinal analysis of a subgroup (n=9) undertaking lifestyle modifications demonstrated that while microbial richness and SCFA production could be significantly improved, responses were highly individualized. These results reveal key functional deficits in the gut microbiome of a typical urban population, reflecting a mismatch with ancestral dietary patterns. The high inter-individual variability in response to changes in dietary patterns challenges one-size-fits-all dietary recommendations and highlights the need for personalized nutritional strategies informed by functional microbiome data.

genomics↗

bioRxiv2025

Exploring the interplay of complex carbohydrate intake, the microbiome CAZymes pool and short-chain fatty acid production in the human gut: insights from different cohorts in the Argentine population

Carbohydrate-active enzyme (CAZyme) activity in the gut microbiome has significant implications for health, including the release of nutrients otherwise inaccessible to the host and the enhancement of digestive efficiency. The primary end products of indigestible carbohydrate fermentation are short-chain fatty acids (SCFAs). We hypothesized that increased dietary fiber consumption could lead to greater SCFA production in the human gut. To investigate this, we examined the relationship between complex carbohydrate intake, CAZyme activity in the human gut microbiome, and SCFA production at the whole metagenomic level across three cohorts: a healthy reference-controlled cohort, an average cohort of individuals living in industrialized cities, and a cohort of patients with inflammatory bowel disease (IBD). Metagenomic sequencing and bioinformatic analyses were utilized to assess the diversity, abundance, and functionality of CAZymes, as well as the metabolic capacity for SCFA production. The average cohort exhibited higher alpha diversity of CAZyme families compared to the reference-controlled cohort, although subfamily composition was similar between both. A moderate negative correlation was identified between CAZyme abundance and SCFA production, indicating that a higher number of these enzymes does not directly translate to increased SCFA synthesis. In IBD patients, a decrease in the diversity and composition of CAZyme subfamilies was observed, suggesting a disruption in enzymatic functions associated with the disease. However, the overall functionality of CAZymes remained relatively stable across different health conditions, highlighting the resilience of the gut microbiome for these functions. These findings deepen our understanding of the gut microbiomes role in health and disease, emphasizing that despite variations in microbial diversity, key enzymatic functions persist. The study underscores the complexity of the non-linear relationship between complex carbohydrate metabolism and SCFA production, laying the groundwork for future research on microbiome-targeted therapeutic/dietary profile interventions in both non-disease and chronic diseases conditions.

genomics↗

bioRxiv2023

Generation of a robust reference gut microbiome dataset for an urban population in Argentina optimized by a machine learning approach

Robust human microbiome analysis requires robust reference datasets obtained from a population that presents similar habits to the one we are trying to assess. We reported here the construction of a robust reference dataset of healthy individuals from urban and surrounding rural areas of the Argentine population. We screened 200 volunteers with strict inclusion/exclusion criteria. Volunteers were also screened with routine blood clinical test analysis and a complete metabolome profile from blood and urine to remove outliers before inclusion in the Next Generation Sequencing dataset. Sequencing was done on an Illumina MiSeq using the V3-V4 16S rRNA. Using these data, we performed de novo community structure prediction by applying clustering methodology based on seven distance and dissimilarity metrics and two clustering methods to the reference set. Using this approach, we discovered four different enterotypes in this community structure. We then trained a model for the classification of any new sample into the structure of the reference set. Once the new sample was classified, it was compared to the reference ranges of both the enterotype-specific subset and the whole reference set. Finally, we challenged the robustness of this methodology using samples from two test case volunteers with clinically proven gut dysbiosis in a time-series sampling with dietary interventions. Our results pointed to the need to carefully analyze the results of gut microbiome in the context of enterotype-specific rather than to a whole population dataset.

microbiology↗

bioRxiv2021

Mechanism of praziquantel action at a parasitic flatworm ion channel

Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is not universally effective, lacking activity against the liver fluke Fasciola. The reason for this insensitivity is unclear, as the mechanism of PZQ action is unknown. Here, we show PZQ activates a transient receptor potential melastatin ion channel (TRPMPZQ) in schistosomes by engaging a hydrophobic ligand binding pocket within the voltage-sensor like domain to cause Ca2+ entry and worm paralysis. PZQ activates TRPMPZQ homologues in other PZQ-sensitive flukes, but not Fasciola. However, a single amino acid change in the Fasciola TRPMPZQ binding pocket, to mimic schistosome TRPMPZQ, confers PZQ sensitivity. After decades of clinical use, the basis of PZQ action at a druggable TRP channel is resolved.

pharmacology and toxicology↗

bioRxiv2019

Building Functional Connectivity Neuromarkers of Behavioral Self-Regulation in Children with and without Autism Spectrum Disorder

Children with Autism Spectrum Disorder (ASD) are known to struggle with behavioral self-regulation, which associates with greater daily-life challenges and an increased risk for psychiatric comorbidities. Despite these negative outcomes, little is known about the neural expression of behavioral regulation in children with and without ASD. Here, we examined whole-brain linear associations between brain functional correlations (FC) and behavioral regulation through connectome predictive modelling (CPM), a data-driven protocol for developing predictive models of brain-behavior relationships from data, assessing neuromarkers using cross-validation. Using data from two sites of the ABIDE II dataset comprising 276 children with and without ASD (8-13 years), we identified functional brain networks whose FC predicted individual differences in two, of three, behavioral regulation subdomains. These distributed network models predicted novel individuals inhibition and shifting from resting-state FC data both in a leave-one-out, as well as split halves, cross-validation. We observed commonalities and differences in the functional networks associating with these subdomains, with inhibition relying on more posterior networks, shifting relying on more anterior networks, and both involving regions of the DMN. Our findings present a substantial addition to our knowledge on the neural expressions of inhibition and shifting across the spectrum of children with and without ASD, demonstrating the utility of this trans-diagnostic modelling approach. Given the numerous cognitive and behavioral issues that can be quantified dimensionally in neurodevelopmental disorders, further refinement of whole-brain neuromarker techniques may thus pave a way for functional neuroimaging to meaningfully contribute to individualized medicine.

neuroscience↗

bioRxiv2017

Case-control study highlights a different gut microbiome in cirrhotic patients with and without hepatocellular carcinoma

BackgroundNo specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported to date.\n\nAimTo compare the gut microbiome found in cirrhotic patients with and without HCC.\n\nMethodsFrom 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition results were also compared with 25 healthy subjects. Faecal stool samples were collected noninvasively, aliquoted for DNA extraction and sequenced for the V3-V4 region of the microbial 16S rRNA (Illumina MiSeq Platform).\n\nResultsThere were no significant clinical differences among cases and controls. We found a differential abundance in family members of Firmicutes with a 3-fold increased of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found 5-fold decreased in HCC versus wo-HCC. The ratio bacteriodes/prevotella was increased in HCC due to the significant decrease in the genus prevotella. Genus Odoribacter and Butyricimonas were more differentialy abundant in HCC. This pattern has been previously associated with an inflammatory milieu with a putative increased activation of NOD-like receptor signalling pathways. A Random Forest model trained with differential abundant taxa correctly classifyed HCC individuals with an error of 22%.\n\nConclusionsA pattern of microbiome linked to inflammation was observed in cirrhotic patients with HCC. These findings open the discussion whether or not microbiota has a physiopathologic role in HCC development in cirrhosis.

cancer biology↗