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- Sjödin, Kotryna Simonyté, et al.
(author)
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Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial
- 2023
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In: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 21:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273. Retrospectively registered on 21 June 2012.
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| 2. |
- Christensen, Andreas, 1987-
(author)
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Capacities, Poincaré inequalities and gluing metric spaces.
- 2023
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Licentiate thesis (other academic/artistic)abstract
- This thesis consists of an introduction, and one research paper with results related to potential theory both in the classical Euclidean setting, as well as in quite general metric spaces.The introduction contains a theoretical and historical background of some basic concepts, and their more modern generalisations to metric spaces developed in the last 30 years. By using upper gradients it is possible to define such notions as first order Sobolev spaces, p-harmonic functions and capacity on metric spaces. When generalising classical results to metric spaces, one often needs to impose some structure on the space by making additional assumptions, such as a doubling condition and a Poincaré inequality.In the included research paper, we study a certain type of metric spaces called bow-ties, which consist of two metric spaces glued together at a single designated point. For a doubling measure μ, we characterise when μ supports a Poincar´e inequality on the bow-tie, in terms of Poincaré inequalities on the separate parts together with a variational p-capacity condition and a quasiconvexity-type condition. The variational p-capacity condition is then characterised by a sharp measure decay condition at the designated point.We also study the special case when the bow-tie consists of the positive and negative hyperquadrants in Rn, equipped with a radial doubling measure. In this setting, we characterise the validity of the p-Poincaré inequality in various ways, and then provide a formula for the variational p-capacity of annuli centred at the origin.i
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| 3. |
- Eriksson, Karolina Ida Anna, et al.
(author)
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Association between Legionella species and humic substances during early summer in the northern Baltic Sea
- 2023
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In: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 9
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Journal article (peer-reviewed)abstract
- Climate change is projected to cause alterations in northern coastal systems, including humification and intensified nutrient loads, which can lead to ecosystem imbalances and establishment of new bacterial species. Several potential pathogens, such as different species of Legionella, hide in the environment between infections, some by living inside protozoan host cells. Knowledge about the occurrence of Legionella in natural waters is missing, which disable risk assessments of exposure. We performed a study of the species diversity of Legionella in the northern Baltic Sea (Gulf of Bothnia) during early summer to map their occurrence and to identify possible environmental drivers. We detected Legionella and potential protozoan hosts along gradients of the Gulf of Bothnia. We also for the first time present third generation full-length 16S rRNA amplicon sequencing (Nanopore) to resolve environmental species classification of Legionella, with a method suitable to study all bacteria. Our data show that full length 16S rRNA sequences is sufficient to resolve Legionella while the standard short Illumina sequences did not capture the entire diversity. For accurate species classification of Legionella, harmonization between the Nanopore classification methods is still needed and the bias toward the well-studied Legionella pneumophila need to be resolved. Different Legionella species occurred both in the Bothnian Sea and in the Bothnian Bay and their abundance were linked to humic substances and low salinity. The relative abundance of Legionella was higher in the humic-rich northern waters of the Bothnian Bay. The link between Legionella species and humic substances may be indirect via promotion of the heterotrophic microbial food web, allowing Legionella species and similar bacteria to establish. Humic substances are rich in iron, which has been shown crucial for growth of Legionella species and other pathogens. Considering climate change projections in this regional area, with increased humification and freshwater inflow, this bacterial niche containing potential pathogens might become more widespread in the future Baltic Sea. This study demonstrates the significance of DNA sequencing to monitor public health relevant bacteria like Legionella species in the environment. Including sequencing of bacteria and protozoa in the environmental monitoring programs could be used to identify ecosystem imbalances, which enable appropriate responses to emerging diseases.
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| 4. |
- Svensson, Daniel, et al.
(author)
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A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences
- 2020
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In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 15:9
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Journal article (peer-reviewed)abstract
- The number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n = 1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n = 300) (ACpop) from Västerbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in Västerbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a Västerbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.
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| 5. |
- Tuiskunen-Bäck, Anne, et al.
(author)
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Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
- 2022
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 766-772
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Journal article (peer-reviewed)abstract
- BACKGROUND: Orthohantaviruses are rodent-borne emerging viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in America. Transmission between humans have been reported and the case-fatality rate ranges from 0.4% to 40% depending on virus strain. There is no specific and efficient treatment for patients with severe HFRS. Here, we characterised a fatal case of HFRS and sequenced the causing Puumala orthohantavirus (PUUV).METHODS: PUUV RNA and virus specific neutralising antibodies were quantified in plasma samples from the fatal case and other patients with non-fatal PUUV infection. To investigate if the causing PUUV strain was different from previously known strains, Sanger sequencing was performed directly from the patient's plasma. Biopsies obtained from autopsy were stained for immunohistochemistry.RESULTS: The patient had approximately tenfold lower levels of PUUV neutralising antibodies and twice higher viral load than was normally seen for patients with less severe PUUV infection. We could demonstrate unique mutations in the S and M segments of the virus that could have had an impact on the severity of infection. Due to the severe course of infection, the patient was treated with the bradykinin receptor inhibitor icatibant to reduce bradykinin-mediated vessel permeability and maintain vascular circulation.CONCLUSIONS: Our data suggest that bradykinin receptor inhibitor may not be highly efficient to treat patients that are at an advanced stage of HFRS. Low neutralising antibodies and high viral load at admission to the hospital were associated with the fatal outcome and may be useful for future predictions of disease outcome.
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