Human gut microbiome studies are mainly bacteria- and archaea-oriented, overlooking the presence of single-cell eukaryotes such as
an enteric stramenopiles with worldwide distribution. Here, we ...surveyed the prevalence and subtype variation of
in faecal samples collected as part of the Flemish Gut Flora Project (FGFP), a Western population cohort. We assessed potential links between
subtypes and identified microbiota-host covariates and quantified microbiota differentiation relative to subtype abundances.
We profiled stool samples from 616 healthy individuals from the FGFP cohort as well as 107 patients with IBD using amplicon sequencing targeting the V4 variable region of the 16S rRNA and 18S rRNA genes. We evaluated associations of
, and their subtypes, with host parameters, diversity and composition of bacterial and archaeal communities.
prevalence in the non-clinical population cohort was 30% compared with 4% among Flemish patients with IBD. Within the FGFP cohort, out of 69 previously identified gut microbiota covariates, only age was associated with
subtype carrier status. In contrast, a strong association between microbiota community composition and
subtypes was observed, with effect sizes larger than that of host covariates. Microbial richness and diversity were linked to both
prevalence and subtype variation. All
subtypes detected in this cohort were found to be less prevalent in
enterotyped samples. Interestingly,
subtypes 3 and 4 were inversely correlated with
, suggesting differential associations of subtypes with host health.
These results emphasise the role of
as a common constituent of the healthy gut microbiota. We show its prevalence is reduced in patients with active IBD and demonstrate that subtype characterisation is essential for assessing the relationship between
, microbiota profile and host health. These findings have direct clinical applications, especially in donor selection for faecal transplantation.
The relationship between gut microbial metabolism and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota-gut-brain communication has ...mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics studies could facilitate the translational process, but their interpretation is hampered by a lack of dedicated reference databases and tools to study the microbial neuroactive potential. Surveying a large microbiome population cohort (Flemish Gut Flora Project, n = 1,054) with validation in independent data sets (n
= 1,070), we studied how microbiome features correlate with host quality of life and depression. Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants. Using a module-based analytical framework, we assembled a catalogue of neuroactive potential of sequenced gut prokaryotes. Gut-brain module analysis of faecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
Abstract
Background
Leptin-deficient
ob/ob
mice and leptin receptor-deficient
db/db
mice are commonly used mice models mimicking the conditions of obesity and type 2 diabetes development. However, ...although
ob/ob
and
db/db
mice are similarly gaining weight and developing massive obesity,
db/db
mice are more diabetic than
ob/ob
mice. It remains still unclear why targeting the same pathway—leptin signaling—leads to the development of two different phenotypes. Given that gut microbes dialogue with the host via different metabolites (e.g., short-chain fatty acids) but also contribute to the regulation of bile acids metabolism, we investigated whether inflammatory markers, bacterial components, bile acids, short-chain fatty acids, and gut microbes could contribute to explain the specific phenotype discriminating the onset of an obese and/or a diabetic state in
ob/ob
and
db/db
mice.
Results
Six-week-old
ob/ob
and
db/db
mice were followed for 7 weeks; they had comparable body weight, fat mass, and lean mass gain, confirming their severely obese status. However, as expected, the glucose metabolism and the glucose-induced insulin secretion were significantly different between
ob/ob
and
db/db
mice. Strikingly, the fat distribution was different, with
db/db
mice having more subcutaneous and
ob/ob
mice having more epididymal fat. In addition, liver steatosis was more pronounced in the
ob/ob
mice than in
db/db
mice. We also found very distinct inflammatory profiles between
ob/ob
and
db/db
mice, with a more pronounced inflammatory tone in the liver for
ob/ob
mice as compared to a higher inflammatory tone in the (subcutaneous) adipose tissue for
db/db
mice. When analyzing the gut microbiota composition, we found that the quantity of 19 microbial taxa was in some way affected by the genotype. Furthermore, we also show that serum LPS concentration, hepatic bile acid content, and cecal short-chain fatty acid profiles were differently affected by the two genotypes.
Conclusion
Taken together, our results elucidate potential mechanisms implicated in the development of an obese or a diabetic state in two genetic models characterized by an altered leptin signaling. We propose that these differences could be linked to specific inflammatory tones, serum LPS concentration, bile acid metabolism, short-chain fatty acid profile, and gut microbiota composition.
Mucositis is a clinically important gastrointestinal inflammatory infirmity, generated by antineoplastic drugs cytotoxic effects. The inflammatory process caused by this disease frequently leads to ...derangements in the alimentary tract and great malaise for the patient. Novel strategies are necessary for its prevention or treatment, as currently available treatments of mucositis have several limitations in relieving its symptoms. In this context, several research groups have investigated the use of probiotic bacteria, and in particular dairy bacterial strains. Compelling evidences reveal that milk fermented by certain probiotic bacteria has the capacity to ameliorate intestinal inflammatory disorders. In addition, innovative probiotic delivery strategies, based on probiotics incorporation into protective matrices, such as whey proteins, were able to increase the therapeutic effect of probiotic strains by providing extra protection for bacteria against environmental stresses. Therefore, in this study, we evaluated the role of the whey protein isolate (WPI), when added to skim milk fermented by
BL23 (
BL23) or by
CIRM-BIA138 (
138), as a protective matrix against
stress challenges. In addition, we investigated the therapeutic effect of these fermented beverages in a murine model of mucositis induced by 5-Fluorouracil (5-FU). Our results demonstrated that milk supplementation with 30% (w/v) of WPI increases the survival rate of both strains when challenged with acid, bile salts, high temperature and cold storage stresses, compared to fermented skim milk without the addition of WPI. Moreover, treatment with the probiotic beverages prevented weight loss and intestinal damages in mice receiving 5-FU. We conclude that the presence of WPI maximizes the anti-inflammatory effects of
BL23, but not for
138, suggesting that whey protein enhancement of probiotic activity might be strain-dependent.
Este artigo apresenta um recorte da pesquisa de conclusão de curso. Nossos objetivos foram investigar como se dão as práticas pedagógicas de professores/as que atuam na Educação não formal em Escolas ...Dominicais de Itambé-BA. Para operacionalização levantamos como objetivos específicos: identificar as práticas pedagógicas dos/as professores/as da Educação não formal em Escolas Dominicais; investigar a formação de professores/as da Escola Dominical; e, refletir sobre os possíveis pontos de contribuição da Pedagogia para a Escola Dominical. A contextualização histórica fundamentou a matriz educacional e educativa desses espaços, na discussão teórica, bem como na compreensão da Pedagogia Social, em suas apropriações e práticas. Os métodos utilizados, neste estudo de caso, foram a análise documental, o questionário e a entrevista semiestruturada. Os resultados demonstram que a Escola Dominical tem uma prática pedagógica coerente, com foco no respeito à faixa etária de cada classe, sendo então uma expressão da Pedagogia Social. Nas considerações apontamos que, ao professor da Escola Dominical, não é exigida uma formação na área de Educação, mas é observada a necessidade de treinamento específico, demonstrando que os conhecimentos formativos da Pedagogia podem favorecer a resolução das dificuldades didático-metodológicas encontradas nessas práticas.
Abstract
While metagenomic sequencing has become the tool of preference to study host-associated microbial communities, downstream analyses and clinical interpretation of microbiome data remains ...challenging due to the sparsity and compositionality of sequence matrices. Here, we evaluate both computational and experimental approaches proposed to mitigate the impact of these outstanding issues. Generating fecal metagenomes drawn from simulated microbial communities, we benchmark the performance of thirteen commonly used analytical approaches in terms of diversity estimation, identification of taxon-taxon associations, and assessment of taxon-metadata correlations under the challenge of varying microbial ecosystem loads. We find quantitative approaches including experimental procedures to incorporate microbial load variation in downstream analyses to perform significantly better than computational strategies designed to mitigate data compositionality and sparsity, not only improving the identification of true positive associations, but also reducing false positive detection. When analyzing simulated scenarios of low microbial load dysbiosis as observed in inflammatory pathologies, quantitative methods correcting for sampling depth show higher precision compared to uncorrected scaling. Overall, our findings advocate for a wider adoption of experimental quantitative approaches in microbiome research, yet also suggest preferred transformations for specific cases where determination of microbial load of samples is not feasible.
Microbial minimal generation times range from a few minutes to several weeks. They are evolutionarily determined by variables such as environment stability, nutrient availability, and community ...diversity. Selection for fast growth adaptively imprints genomes, resulting in gene amplification, adapted chromosomal organization, and biased codon usage. We found that these growth-related traits in 214 species of bacteria and archaea are highly correlated, suggesting they all result from growth optimization. While modeling their association with maximal growth rates in view of synthetic biology applications, we observed that codon usage biases are better correlates of growth rates than any other trait, including rRNA copy number. Systematic deviations to our model reveal two distinct evolutionary processes. First, genome organization shows more evolutionary inertia than growth rates. This results in over-representation of growth-related traits in fast degrading genomes. Second, selection for these traits depends on optimal growth temperature: for similar generation times purifying selection is stronger in psychrophiles, intermediate in mesophiles, and lower in thermophiles. Using this information, we created a predictor of maximal growth rate adapted to small genome fragments. We applied it to three metagenomic environmental samples to show that a transiently rich environment, as the human gut, selects for fast-growers, that a toxic environment, as the acid mine biofilm, selects for low growth rates, whereas a diverse environment, like the soil, shows all ranges of growth rates. We also demonstrate that microbial colonizers of babies gut grow faster than stabilized human adults gut communities. In conclusion, we show that one can predict maximal growth rates from sequence data alone, and we propose that such information can be used to facilitate the manipulation of generation times. Our predictor allows inferring growth rates in the vast majority of uncultivable prokaryotes and paves the way to the understanding of community dynamics from metagenomic data.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for ...(meta-)genomic data analysis, we studied species-function relationships in gut microbial genomes and microbiomes. Half of gut-associated species were found to be generalists regarding overall substrate preference, but we observed significant genus-level metabolic diversification linked to bacterial life strategies. Within each genus, metabolic consistency varied significantly, being low in Firmicutes genera and higher in Bacteroides. Differentiation of fermentable substrate degradation potential contributed to metagenomic functional repertoire variation between individuals, with different enterotypes showing distinct saccharolytic/proteolytic/lipolytic profiles. Finally, we found that module-derived functional redundancy was reduced in the low-richness Bacteroides enterotype, potentially indicating a decreased resilience to perturbation, in line with its frequent association to dysbiosis. These results provide insights into the complex structure of gut microbiome-encoded metabolic properties and emphasize the importance of functional and ecological assessment of gut microbiome variation in clinical studies.
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