| 1. |
- Das, Promi, 1990, et al.
(författare)
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Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome
- 2019
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Human gut microbial communities have been known to produce vitamins, which are subsequently absorbed by the host in the large intestine. However, the relationship between species with vitamin pathway associated with functional features or their gene abundance in different states of health and disease is lacking. Here, we analyzed shotgun fecal metagenomes of individuals from four different countries for genes that are involved in vitamin biosynthetic pathways and transport mechanisms and corresponding species’ abundance. Results We found that the prevalence of these genes was found to be distributed across the dominant phyla of gut species. The number of positive correlations was high between species harboring genes related to vitamin biosynthetic pathways and transporter mechanisms than that with either alone. Although the range of total gene abundances remained constant across healthy populations at the global level, species composition and their presence for metabolic pathway related genes determine the abundance and functional genetic content of vitamin metabolism. Based on metatranscriptomics data, the equation between the abundance of vitamin-biosynthetic enzymes and vitamin-dependent enzymes suggests that the production and utilization potential of these enzymes seems way more complex usage allocations than just mere direct linear associations. Conclusions Our findings provide a rationale to examine and disentangle the interrelationship between B-vitamin dosage (dietary or microbe-mediated) on gut microbial members and the host, in the gut microbiota of individuals with under- or overnutrition.
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| 2. |
- Kumar, Manish, 1982, et al.
(författare)
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Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling
- 2018
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Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 49, s. 128-142
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Tidskriftsartikel (refereegranskat)abstract
- Malnutrition is a severe non-communicable disease, which is prevalent in children from low-income countries. Recently, a number of metagenomics studies have illustrated associations between the altered gut microbiota and child malnutrition. However, these studies did not examine metabolic functions and interactions between individual species in the gut microbiota during health and malnutrition. Here, we applied genome-scale metabolic modeling to model the gut microbial species, which were selected from healthy and malnourished children from three countries. Our analysis showed reduced metabolite production capabilities in children from two lowincome countries compared with a high-income country. Additionally, the models were also used to predict the community-level metabolic potentials of gut microbes and the patterns of pairwise interactions among species. Hereby we found that due to bacterial interactions there may be reduced production of certain amino acids in malnourished children compared with healthy children from the same communities. To gain insight into alterations in the metabolism of malnourished (stunted) children, we also performed targeted plasma metabolic profiling in the first 2 years of life of 25 healthy and 25 stunted children. Plasma metabolic profiling further revealed that stunted children had reduced plasma levels of essential amino acids compared to healthy controls. Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition.
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| 3. |
- Babaei, Parizad, 1990, et al.
(författare)
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Challenges in modeling the human gut microbiome
- 2018
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 36:8, s. 682-686
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Babaei, Parizad, 1990
(författare)
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In silico analysis of microbial communities through constraint-based metabolic modelling
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microbial communities are involved in many vital biological processes from elemental cycles to sustaining human health. The bacterial assemblages are remarkably under-studied as they are reluctant to grow in the laboratory conditions. Therefore, alternative omics-based approaches and computational modelling methods have been an active area of research to investigate microbial communities physiologically, ecologically and biochemically. In this thesis different microbial consortia involved in food production and also the human gut microbiota have been modelled and investigated. In the case of the human gut microbiota, the effects of malnutrition on the overall health of children from three different countries, namely, Malawi and Bangladesh, and Sweden have been studied. In each of the first two countries, a group of malnourished children going through food therapy as well as a healthy cohort were monitored to investigate the effect of food intervention on malnutrition, with their gut microbiota being the focal point. In this project, using metagenomics data we identified the dominant strains in each cohort, reconstructed genome-scale metabolic models (GEMs) for the most abundant ones and used our models to predict diet-microbe, microbe-microbe, and microbe- host interactions. Based on our results in this project, in addition to being less diverse, the gut microbiota of malnourished children showed a lower potency regarding the production of valuable metabolites. The second investigated microbial consortia were the ones used in fermented milk products. Based on the genome sequence and also experimental data for five selected strains, we reconstructed GEMs, curated the models and performed community modelling to predict their metabolic interactions. Using the simulation outcomes, we could predict a ratio for bacterial strains used in yogurt starter culture to maximise the production of acetaldehyde which is a key contributor to yogurt’s unique taste and aroma. GEMs are powerful tools to model an organism’s metabolic capabilities, and although numerous GEMs have been reconstructed, their quality control has not gained enough attention. Evaluation of a repository of semi-automatically reconstructed GEMs related to the human gut microbiota and another repository of manually curated ones was performed comparatively. Assessing these models from topological and functional aspects, it was shown that semi-automatically reconstructed models required extensive manual curation before they could be used for target-specific simulations. In constraint-based modelling, an objective function is usually optimised under particular environmental conditions, however, in case of the microbial communities, there is no distinct and relevant objective function. Therefore, an unbiased uniform randomised sampling algorithm was implemented for microbial communities. The samples acquired from the solution space were analysed statistically to see clustering patterns of the reactions and commensalistic relationships between the community members were identified. Overall, computational modelling paves the way towards gaining a mechanistic understanding of microbial communities and provides us with testable hypotheses and insight.
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| 5. |
- Kumar, Manish, 1982, et al.
(författare)
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Human gut microbiota and healthy aging: Recent developments and future prospective
- 2016
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Ingår i: Nutrition and healthy aging. - 2451-9480. ; 4:1, s. 3-16
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Tidskriftsartikel (refereegranskat)abstract
- The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics.
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| 6. |
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