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Alm, E.

Publications and source records attributed to Alm, E..

8 recordsLinked to original sources

Variation in gut microbiome diversity and structure across host lifestyles in Thailand

Global comparisons have revealed marked shifts in gut microbiome diversity and composition with industrialization and urbanization. Whether such changes also arise at finer geographical scales, among neighboring populations adopting different lifestyles, remains largely unexplored. In this study, we characterized the gut microbiomes of Thai populations with distinct lifestyles: urban residents from Bangkok, farmers from Tak province, and foragers from Phatthalung province. Our results reveal that microbiomes of all populations are primarily dominated by the families Prevotellaceae, Bacteroidaceae, and Lachnospiraceae, yet their specific abundances differ between populations. -diversity, particularly Faiths phylogenetic diversity, showed a descending trend from the rural to urban populations. Despite these differences, results suggested that most highly prevalent microbial genera were shared among all groups, suggesting the existence of a consistent core microbiome within the Thai population, despite differing lifestyles. Further, association analysis shows that overall population-wide lifestyle was significantly associated with microbial community structure, explaining 0.5-4% of the variation depending on the {beta}-diversity metrics. Linking dietary habits and other lifestyle factors to genus abundance revealed population-specific microbiome-lifestyle associations, indicating that baseline microbial community composition determines microbiome variability in response to environmental changes. Overall, our study expands the scope of lifestyle-microbiome research and identifies associations between lifestyle and microbial features, underscoring the influence of lifestyle factors and baseline microbiomes on microbial compositional adaptation.

microbiology↗

Host transcriptional responses to gut microbiome variation arising from urbanism

Gut microbiomes of urban communities are compositionally different from their rural counterparts, and are associated with immune dysregulation and gastrointestinal disease. However, it is unknown whether these compositional differences impact host physiology, and through what mechanisms. Here, we used human colonic epithelial cells to directly compare host transcriptional changes induced by gut microbiomes from urban versus rural communities. We co-cultured host cells with live, stool-derived gut microbiomes from Rwanda, Ghana, Nigeria, Malaysia, and the United States, and quantified transcriptional responses using RNA-seq. We found that urban microbiomes affected innate immune pathways, including TNF signaling and bacterial antigen recognition. We also found that high-diversity microbiomes elicited a stronger host transcriptional response, while low-diversity microbiomes triggered epithelial restructuring and glycolysis. Finally, specific taxa driving these effects, including Bifidobacterium adolescentis and Bacteroides dorei, correlated with lifestyle factors such as diet. These findings demonstrate that urbanization-associated microbiome changes directly influence host epithelial gene expression.

microbiology↗

Bifidobacterium longum subsp. nexus nov., a novel subspecies isolated from infant stool

Bifidobacterium longum is a foundational, genetically diverse member of the infant gut microbiome, yet resolving its subspecies in metagenomic data remains challenging. Here, we performed a deep phylogenetic characterization of the B. longum species utilizing 4,577 fecal metagenomes from the LLNEXT mother-infant cohort alongside a global dataset of 1,220 genomes and metagenome-assembled genomes (MAGs). We identified a novel, geographically widespread lineage: Bifidobacterium longum subsp. nexti. Using a polyphasic taxonomic analysis, including average nucleotide identity and digital DNA-DNA hybridization, confirms subspecies-level divergence. Distinct from other members of the B. longum species, BL. nexti harbors -amylopullulanase and grows on soluble starch and often pullulan, consistent with -glucan utilization. Within the LLNEXT cohort, BL. nexti is enriched in formula-fed infants and shows evidence consistent with vertical transmission. Globally, while BL. nexti is geographically widespread, it usually persists at low relative abundance across diverse populations. By resolving a major fraction of previously unclassified B. longum diversity, this study provides new insights into the specialized lineages and ecological dynamics driving the assembly of the developing infant microbiome.

microbiology↗

High genome plasticity and frequent genetic exchange in Leishmania tropica isolates from Afghanistan, Iran and Syria

BackgroundThe kinetoplastid protozoan Leishmania tropica mainly causes cutaneous leishmaniasis in humans in the Middle East, and relapse or treatment failure after treatment are common in this area. L. tropicas digenic life cycle includes distinct stages in the vector sandfly and the mammalian host. Sexual reproduction and genetic exchange appear to occur more frequently than in other Leishmania species. Understanding these processes is complicated by chromosome instability during cell division that yields aneuploidy, recombination and heterozygosity. This combination of rare recombination and aneuploid permits may reveal signs of hypothetical parasexual mating, where diploid cells fuse to form a transient tetraploid that undergoes chromosomal recombination and gradual chromosomal loss. Methodology/Principal FindingsThe genome-wide SNP diversity from 22 L. tropica isolates showed chromosome-specific runs of patchy heterozygosity and extensive chromosome copy number variation. All these isolates were collected during 2007-2017 in Sweden from patients infected in the Middle East and included isolates from a patient possessing two genetically distinct leishmaniasis infections three years apart with no evidence of re-infection. We found differing ancestries on the same chromosome (chr36) across multiple samples: matching the reference genome with few derived alleles, followed by blocks of heterozygous SNPs, and then by clusters of homozygous SNPs with specific recombination breakpoints at an inferred origin of replication. Other chromosomes had similar marked changes in heterozygosity at strand-switch regions separating polycistronic transcriptional units. Conclusion/SignificanceThese large-scale intra- and inter-chromosomal changes in diversity driven by recombination and aneuploidy suggest multiple mechanisms of cell reproduction and diversification in L. tropica, including mitotic, meiotic and parasexual processes. It underpins the need for more genomic surveillance of Leishmania, to detect emerging hybrids that could spread more widely and to better understand the association between genetic variation and treatment outcome. Furthering our understanding of Leishmania genome evolution and ancestry will aid better diagnostics and treatment for cutaneous leishmaniasis caused by L.tropica in the Middle East. Author SummaryCutaneous leishmaniasis is mainly caused by Leishmania tropica in the Middle East, where it is known for treatment failure and a need for prolonged and/or multiple treatments. Several factors affect the clinical presentation and treatment outcome, such as host genetic variability and specific immune response, as well as environmental factors and the vector species. Little is known about the parasite genome and its influence on treatment response. By analysing the genome of 22 isolates of L. tropica, we have revealed extensive genomic variation and a complex population structure with evidence of genetic exchange within and among the isolates, indicating a possible presence of sexual or parasexual mechanisms. Understanding the Leishmania genome better may improve future treatment and better understanding of treatment failure and relapse.

genetics↗

Prebiotics and community composition influence gas production of the human gut microbiota

Prebiotics confer benefits to human health often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a byproduct of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota is affected by the chemical composition of the prebiotic and by the composition of the microbiota. We first constructed a linear systems model based on mass and electron balance and compared the theoretical product range of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while inter-individual differences in H2 production during inulin degradation was driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production will depend more on substrate, while rare metabolisms like methanogenesis depend more strongly on microbiome composition. ImportancePrebiotic fermentation in the gut often leads to the co-production of short chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely taken into account during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production was strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production was less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

microbiology↗

Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function

11.1 BackgroundChildren with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration.\n\n1.2 MethodsWe conducted a prospective cohort study of 222 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected and 16S sequencing was performed. A subset of patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. Microbial communities across the aerodi-gestive tract were compared in patients with and without aspiration by calculating within-patient beta diversities and quantifying microbial exchange across sites.\n\n1.3 ResultsWithin all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.55 and 0.56, respectively; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 3x10-5, respectively).\n\n1.4 ConclusionsThe gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swal-low function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.

microbiology↗

Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal

Interest in manipulating the gut microbiota to treat disease has led to a need for understanding how organisms can establish themselves when introduced into a host with an intact microbial community. While probiotic or prebiotic approaches typically lead to a transient pulse in an organisms abundance, persistent establishment of an introduced species may require alternative strategies. Here, we introduce the concept of orthogonal niche engineering in the gut, where we include a resource typically absent from the diet, seaweed, to establish a customized niche for an introduced organism. We show that in the short term, co-introduction of this resource at 1% in the diet along with an organism with exclusive access to this resource, B. plebeius DSM 17135, enables it to colonize at a median abundance of 1%, frequently increasing in abundance to 10 or more percent. We construct a mathematical model of the system to infer that B. plebeius competitively acquires endogenous resources. We provide evidence that it competes with native commensals to achieve its observed abundance. We observe a diet-dependent loss in seaweed responsiveness of B. plebeius in the long term and show the potential for IgA-mediated control of putative invaders by the immune system. These results point to the potential for diet-based intervention as a means to introduce target organisms, but also indicate potential modes for failure of this strategy in the long term.

microbiology↗

Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort

Dietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a hosts microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patients microbiota.

microbiology↗