| 1. |
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| 2. |
- Alevronta, Eleftheria, et al.
(author)
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Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.
- 2018
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 57:10, s. 1352-1358
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Journal article (peer-reviewed)abstract
- To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future.From a larger group of gynecological cancer survivors followed-up 2-14years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models.The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3Gy, γ50=1.19 for all models, s was 7.0e-09 for RS and n was 9.9×107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB.Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.
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| 3. |
- Alin, Rebecca, 1989, et al.
(author)
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A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy
- 2021
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In: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
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Journal article (peer-reviewed)abstract
- Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.
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| 4. |
- Bankvall, Maria, et al.
(author)
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The oral microbiota of patients with recurrent aphthous stomatitis.
- 2014
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In: Journal of oral microbiology. - : Informa UK Limited. - 2000-2297. ; 6
-
Journal article (peer-reviewed)abstract
- Specific pathogenic bacteria have been implicated in recurrent aphthous stomatitis (RAS), a chronic inflammatory condition characterised by ulcerations in the oral mucosa. However, the aetiology behind this condition still remains unclear.
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| 5. |
- Barman, Malin, 1983, et al.
(author)
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Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden
- 2018
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In: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 8:10
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Journal article (peer-reviewed)abstract
- © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health.METHODS AND ANALYSIS: The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health.ETHICS AND DISSEMINATION: The NICE cohort has been approved by the Regional Ethical Review Board in Umeå, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.
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| 6. |
- Bull, Cecilia, 1977, et al.
(author)
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A novel mouse model of radiation-induced cancer survivorship diseases of the gut
- 2017
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In: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 313:5, s. G456-G466
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Journal article (peer-reviewed)abstract
- A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury. NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury.
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| 7. |
- Bull, Cecilia, 1977, et al.
(author)
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Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy
- 2024
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In: ADVANCES IN RADIATION ONCOLOGY. - 2452-1094. ; 9:1
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Journal article (peer-reviewed)abstract
- Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation -induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation -induced intestinal syndromes: urgency-tenesmus syndrome, fecal -leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient -reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecalleakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation -induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.
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| 8. |
- Dafar, Amal, et al.
(author)
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Lingual microbiota profiles of patients with geographic tongue
- 2017
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In: Journal of Oral Microbiology. - : Informa UK Limited. - 2000-2297. ; 9:1
-
Journal article (peer-reviewed)abstract
- Geographic tongue (GT) is an oral mucosal lesion that affects the tongue. The association between GT and the bacterial colonization profiles of the tongue is not clear. Lingual swabs were collected from lesion sites and healthy sites of 35 patients with GT (19 males and 16 females; M-age = 54.3 +/- 16.1 years) and 22 controls (12 males and 10 females; M-age = 56.3 +/- 15.8 years). Bacterial DNA was extracted and sequenced by next-generation sequencing. At the phylum level, Fusobacteria were significantly less abundant, while Spirochaetes were significantly more abundant in GT patients compared to controls. At the operational taxonomic units level, multivariate analysis revealed distinct clusters for the three groups based on the lingual microbiota composition. Acinetobacter and Delftia were significantly associated with GT lesion and healthy sites. However, Microbacterium, Leptospira, Methylotenera, and Lactococcus were significantly associated with GT lesion sites. Additionally, Mogibacterium and Simonsiella were significantly associated with GT healthy sites and controls. The changes in the lingual microbiota profiles of patients with GT imply a shift in the lingual bacterial ecology. However, it remains unknown if this shift is a consequence of the lesions or of factors associated with the initiation and progression of the disease.
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| 9. |
- Devarakonda, Sravani, et al.
(author)
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Dietary Fiber and the Hippocampal Neurogenic Niche in a Model of Pelvic Radiotherapy
- 2021
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In: Neuroscience. - : Elsevier BV. - 0306-4522. ; 475, s. 137-147
-
Journal article (peer-reviewed)abstract
- sought to determine whether radiation to the colorectum had an impact on parameters of hippocampal neurogenesis and, if so, whether it could be modulated by a fiber-rich diet. Male C57BL/6J mice were fed a diet containing bioprocessed oat bran or a fiber-free diet, starting two weeks before colorectal irradiation with 4 fractions of 8 Gray or sham-irradiation. Diets were then continued for 1, 6 or 18 weeks, whereafter parameters of hippocampal neurogenesis were analyzed and correlated to serum cytokine levels. No statistically significant changes in neuronal markers or cell proliferation were found at one week post-irradiation. Six weeks postirradiation there was a decreased cell proliferation in the subgranular zone that appeared slightly more pronounced in irradiated animals on a fiber-free diet and increased numbers of immature neurons per mm2 dentate gyrus in the irradiated mice, with a statistically significant increase in mice on a fiber-rich diet. Microglial abundancy was similar between all groups. 18 weeks post-irradiation, a fiber-free diet had reduced the number of immature neurons, whereas irradiation resulted in an increase. Despite this, the population of mature neurons was stable. Analysis of serum cytokines revealed a negative correlation between MIP1-a and the number of immature neurons one week after irradiation, regardless of diet. Our findings show that pelvic radiotherapy has the potential to cause a long-lasting impact on hippocampal neurogenesis, and dietary interventions may modulate this impact. More in-depth studies on the relationship between irradiation-induced intestinal injury and brain health are warranted. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 10. |
- Gio-Batta, Monica, et al.
(author)
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Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema.
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
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| 11. |
- Hedelin, Maria, 1964, et al.
(author)
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Intake of citrus fruits and vegetables and the intensity of defecation urgency syndrome among gynecological cancer survivors.
- 2019
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 14:1
-
Journal article (peer-reviewed)abstract
- Despite the experimental evidence that certain dietary compounds lower the risk of radiation-induced damage to the intestine, clinical data are missing and dietary advice to irradiated patients is not evidence-based.We have previously identified 28 intestinal health-related symptoms among 623 gynaecological-cancer survivors (three to fifteen years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five radiation-induced survivorship syndromes: defecation-urgency syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge and blood discharge. The grouping was based on factor scores produced by Exploratory Factor Analysis in combination with the Variable Cutoff Method. Frequency of food intake was measured by a questionnaire. We evaluated the relationship between dietary intake and the intensity of the five syndromes.With the exception of excessive mucus discharge, the intensity of all syndromes declined with increasing intake of citrus fruits. The intensity of defecation-urgency and fecal-leakage syndrome declined with combined intake of vegetables and citrus fruits. The intensity of excessive mucus discharge was increased with increasing intake of gluten.In this observational study, we found an association between a high intake of citrus fruits and vegetables and a lower intensity of the studied radiation-induced cancer survivorship syndromes. Our data suggest it may be worthwhile to continue to search for a role of the diet before, during and after radiotherapy to help the cancer survivor restore her or his intestinal health after irradiation.
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| 12. |
- Hesselmar, Bill, 1955, et al.
(author)
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Pacifier Cleaning Practices and Risk of Allergy Development.
- 2013
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:6
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Immune stimulation through exposure to commensal microbes may protect against allergy development. Oral microbes may be transferred from parents to infants via pacifiers. We investigated whether pacifier cleaning practices affected the risk of allergy development.METHODS:A birth-cohort of 184 infants was examined for clinical allergy and sensitization to airborne and food allergens at 18 and 36 months of age and, in addition, promptly on occurrence of symptoms. Pacifier use and pacifier cleaning practices were recorded during interviews with the parents when the children were 6 months old. The oral microbiota of the infants was characterized by analysis of saliva samples collected at 4 months of age.RESULTS:Children whose parents "cleaned" their pacifier by sucking it (n = 65) were less likely to have asthma (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.01-0.99), eczema (OR 0.37; 95% CI 0.15-0.91), and sensitization (OR 0.37; 95% CI 0.10-1.27) at 18 months of age than children whose parents did not use this cleaning technique (n = 58). Protection against eczema remained at age 36 months (hazard ratio 0.51; P = .04). Vaginal delivery and parental pacifier sucking yielded independent and additive protective effects against eczema development. The salivary microbiota differed between children whose parents cleaned their pacifier by sucking it and children whose parents did not use this practice.CONCLUSIONS:Parental sucking of their infant's pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent's saliva.
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| 13. |
- Malipatlolla, Dilip, 1990, et al.
(author)
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A fiber-rich diet and radiation-induced injury in the murine intestinal mucosa
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:1
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Journal article (peer-reviewed)abstract
- Dietary fiber is considered a strong intestinal protector, but we do not know whether dietary fiber protects against the long-lasting mucosal damage caused by ionizing radiation. To evaluate whether a fiber-rich diet can ameliorate the long-lasting pathophysiological hallmarks of the irradiated mucosa, C57BL/6J mice on a fiber-rich bioprocessed oat bran diet or a fiber-free diet received 32 Gray in four fractions to the distal colorectum using a linear accelerator and continued on the diets for one, six or 18 weeks. We quantified degenerating crypts, crypt fission, cell proliferation, crypt survival, macrophage density and bacterial infiltration. Crypt loss through crypt degeneration only occurred in the irradiated mice. Initially, it was most frequent in the fiber-deprived group but declined to levels similar to the fiber-consuming group by 18 weeks. The fiber-consuming group had a fast response to irradiation, with crypt fission for growth or healing peaking already at one week post-irradiation, while crypt fission in the fiber-deprived group peaked at six weeks. A fiber-rich diet allowed for a more intense crypt cell proliferation, but the recovery of crypts was eventually lost by 18 weeks. Bacterial infiltration was a late phenomenon, evident in the fiber-deprived animals and intensified manyfold after irradiation. Bacterial infiltration also coincided with a specific proinflammatory serum cytokine profile. In contrast, mice on a fiber-rich diet were completely protected from irradiation-induced bacterial infiltration and exhibited a similar serum cytokine profile as sham-irradiated mice on a fiber-rich diet. Our findings provide ample evidence that dietary fiber consumption modifies the onset, timing and intensity of radiation-induced pathophysiological processes in the intestinal mucosa. However, we need more knowledge, not least from clinical studies, before this finding can be introduced to a new and refined clinical practice.
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| 14. |
- Malipatlolla, Dilip, 1990, et al.
(author)
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Long-term mucosal injury and repair in a murine model of pelvic radiotherapy
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction. We then determined the long-term dynamics of mucosal injury, repair, and the duration of inflammation. We show that crypt fission, not cell proliferation, is the main long-term mechanism for rescuing crypt density after irradiation, and provides a potentially wide window for clinical interventions. Persisting macrophage aggregations indicate a chronic mucosal inflammation. A better understanding as to how crypt fission is triggered and why it fails to repair fully the mucosa may help restore bowel health after pelvic radiotherapy. Moreover, anti-inflammatory interventions, even if implemented long after completed radiotherapy, could promote bowel health in pelvic cancer survivors.
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| 15. |
- Mayer Labba, Cecilia, 1987, et al.
(author)
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Isolation, identification, and selection of strains as candidate probiotics and starters for fermentation of Swedish legumes
- 2020
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In: Food and Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 64, s. 4410-13
-
Journal article (peer-reviewed)abstract
- Background : The non-dairy sector is growing, fermented alternatives to dairy are sparse. Adapted starter cultures to substituting raw materials needs to be developed. Objective : Aims of this study were to isolate, identify, and phenotypically characterize lactic acid bacteria (LAB) that inhabit Swedish legumes, and assess properties necessary for selecting strains with the ability to ferment a bean beverage and with potential health beneficial properties. Design : Isolates of presumed LAB were obtained from legumes collected at Öland, Sweden. Strain diversity was assessed by repetitive polymerase chain reaction (rep-PCR). The strains were identified using matrix- assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS). Species belonging to Enterococcus were predominant along with Pediococcus and closely related Bacillus. Strains were tested for tolerance to low pH, phenol, and bile as well as their bile salt hydrolase (BSH) activity. In addition, Enterococcus strains were tested for antibiotic resistance, and Pediococcus strains for their ability to ferment a bean beverage. Results : From the 25 strains char acterized, five were found resistant to low pH, bile, and phenol, suggesting that they can survive a passage through the gastrointestinal tract (GIT) and hence potentially exert beneficial effects in the host. These are suggested for further investigation on specific host-beneficial properties. Two of these, belonging to Pediococ cus pentosaceus, were able to ferment a bean beverage without any added nutrients, indicating that the Pediococcus strains are well adapted to the bean substrate. One of the P. pentosaceus strains were also able to markedly improve the reduction of phytate by the phytase-producing yeast strain Pichia kudriavzevii TY1322 during co-fermentation as well as increase the final cell count of the yeast strain. Conclusion : Strain isolation and characterization performed in this study aids in selecting starter cultures for legume fermentation. Nutritional properties can be improved by co-fermentation with yeast indicating that novel nutritious fermented non-dairy products could be developed.
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| 16. |
- Nyberg, Lena, 1979, et al.
(author)
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Optical mapping of single DNA molecules in nanochannels: A novel method for identification and characterization of antibiotic resistance
- 2015
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In: 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014. - 9780979806476 ; , s. 1045-1047
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Conference paper (peer-reviewed)abstract
- The use, and overuse, of antibiotics has during the last decade led to a dramatic increase in antibiotic resistance and there is a crying need for novel methods for fast identification of antibiotic resistance genes. We here demonstrate how our previously developed assay for optical mapping of DNA in nanochannels can be used for characterization of resistance genes located on plasmid DNA from bacteria. The assay requires extremely small sample volumes and does neither rely on PCR, nor culturing of bacteria, which greatly reduces the time for analysis.
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| 17. |
- Patel, Piyush, et al.
(author)
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Dietary oat bran reduces systemic inflammation in mice subjected to pelvic irradiation
- 2020
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 12:8
-
Journal article (peer-reviewed)abstract
- Patients undergoing radiotherapy to treat pelvic-organ cancer are commonly advised to follow a restricted fiber diet. However, reducing dietary fiber may promote gastrointestinal inflammation, eventually leading to deteriorated intestinal health. The goal of this study was to evaluate the influence of dietary fiber on radiation-induced inflammation. C57BL/6J male mice were fed a High-oat bran diet (15% fiber) or a No-fiber diet (0% fiber) and were either irradiated (32 Gy delivered in four fractions) to the colorectal region or only sedated (controls). The dietary intervention started at 2 weeks before irradiation and lasted for 1, 6, and 18 weeks after irradiation, at which time points mice were sacrificed and their serum samples were assayed for 23 cytokines and chemokines. Our analyses show that irradiation increased the serum cytokine levels at all the time points analyzed. The No-fiber irradiated mice had significantly higher levels of pro-inflammatory cytokines than the High-oat irradiated mice at all time points. The results indicate that a fiber-rich oat bran diet reduces the intensity of radiation-induced inflammation, both at an early and late stage. Based on the results, it seems that the advice to follow a low-fiber diet during radiotherapy may increase the risk of decreased intestinal health in cancer survivors. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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| 18. |
- Rabe, Hardis, et al.
(author)
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Neonatal gut colonization by Bifidobacterium is associated with higher childhood cytokine responses.
- 2020
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In: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 12:1, s. 1-14
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Journal article (peer-reviewed)abstract
- The gut microbiota is a major stimulus for the immune system, and late acquisition of bacteria and/or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is unknown how the gut bacterial colonization pattern in human infants is related to T cell activation during early childhood. We followed 65 Swedish children in the FARMFLORA cohort, from birth up to 3years of age. In fecal samples collected at several time points during the first year of life, the gut colonization pattern was investigated with the use of both 16S rRNA next generation sequencing (NGS) and culture-based techniques. This was related to production of IL-13, IL-5, IL-6, TNF, IL-1β and IFN-γ by PHA-stimulated fresh mononuclear cells and to proportions of CD4+ T cells that expressed CD45RO at 36months of age. Both NGS and culture-based techniques showed that colonization by Bifidobacterium at 1week of age associated with higher production of IL-5, IL-6, IL-13, TNF and IL-1β at 36months of age. By contrast, gut colonization by Enterococcus, Staphylococcus aureus or Clostridium in early infancy related inversely to induced IL-13, IL-5 and TNF at 3years of age. Infants with elder siblings produced more cytokines and had a larger fraction of CD45RO+ T cells compared to single children. However, controlling for these factors did not abolish the effect of colonization by Bifidobacterium on immune maturation. Thus, gut colonization in early infancy affects T cell maturation and Bifidobacterium may be especially prone to induce infantile immune maturation.
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| 19. |
- Rangel, Ignacio, 1969-, et al.
(author)
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Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of G alpha i2-deficient mice
- 2016
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In: Fems Microbiology Ecology. - Oxford, United Kingdom : Oxford University Press (OUP). - 0168-6496 .- 1574-6941. ; 92:7
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Journal article (peer-reviewed)abstract
- An altered immune response and gut microbiota have been associated with the pathology of inflammatory bowel diseases (IBDs). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (G alpha i2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus. High gene expression levels of IL-17 and IFN-gamma in colon and caecum were detected in G alpha i2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-gamma and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.
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| 20. |
- Sjöberg, Fei, et al.
(author)
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Are all faecal bacteria detected with equal efficiency? A study using next-generation sequencing and quantitative culture of infants' faecal samples
- 2020
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In: Journal of Microbiological Methods. - : Elsevier BV. - 1872-8359 .- 0167-7012. ; 177
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Journal article (peer-reviewed)abstract
- Background: Many species of intestinal bacteria are present in moderate numbers in the faecal microbiota, which is dominated by obligate anaerobes. Little is known regarding the detection sensitivity of next-generation sequencing for these microbes in samples of complex microbiota. Methods: Twenty stool samples from six healthy infants, who were followed from 1 week to 1 year of age, were previously cultured quantitatively for total population counts, as well as for counts of relevant facultative bacteria and a limited selection of obligate anaerobes that are prevalent in the neonatal microbiota. The same samples were analysed by Next-generation sequencing (NGS, pyrosequencing) of the 16S rRNA gene (V1–V3 regions; average read length, 500 nucleotides; average number of reads per sample, 30,000). We used the bacterial culture data to determine the lowest bacterial populations that could be detected by NGS. Different DNA extraction kits (QIAamp DNA Stool Mini, ZR Faecal DNA MiniPrep, and PowerSoil DNA Isolation) were compared for efficacy in extracting DNA from Gram-negative and Gram-positive Type strains. Results: NGS yielded one read per 106 CFU/g faeces of the Gram-negative commensal gut bacteria Bacteroides and Enterobacteriaceae, but only one read per 108 CFU/g faeces of Gram-positive bifidobacteria. The Gram-positive facultative bacteria Enterococcus was often undetectable by DNA-based methods despite being present at >106 CFU/g faeces. The DNA extraction kits tested varied considerably in their ability to extract DNA from bacterial samples, and showed considerably lower efficacies in extracting DNA from Gram-positive than from Gram-negative bacteria. Conclusions: NGS has lower sensitivity for detecting Gram-positive bacteria than Gram-negative bacteria, due at least in part to inefficient extraction of DNA from Gram-positive bacteria. Therefore, enzymatic lysis may enhance the yield of DNA and increase the sensitivity of NGS methods for Gram-positive bacteria, and the inclusion of positive and negative controls during DNA extraction is indicated for validation purposes. The differential extraction of DNA from bacterial samples by different DNA extraction kits may limit comparability between studies on the gut microbiota. Finally, quantitative culture methods detect certain bacteria with greater sensitivity than NGS techniques, and thus culture- and DNA-based methods can be used in tandem to define the complex composition of the gut microbiota with greater accuracy.
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| 21. |
- Sjöberg, Fei, et al.
(author)
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Comparison between terminal-restriction fragment length polymorphism (T-RFLP) and quantitative culture for analysis of infants' gut microbiota
- 2013
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In: Journal of Microbiological Methods. - : Elsevier BV. - 0167-7012 .- 1872-8359. ; 94:1, s. 37-46
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Journal article (peer-reviewed)abstract
- The infantile intestinal microbiota is a major stimulus for immune maturation. Both culture and DNA-based methods can be used for microbiota characterization, but few studies have systematically compared their performance for analysis of the gut microbiota. Here, we examined fecal samples obtained on six occasions between one week and 12 months of age from six vaginally delivered infants. After quantitative aerobic and anaerobic culture of the samples on selective and non-selective media, DNA was extracted from the fecal samples and analyzed regarding 16S rRNA gene polymorphism by terminal-restriction fragment length polymorphism (T-RFLP). A database was constructed for direct identification of T-RFLP peaks by analysis of pure-culture bacteria and analysis of a limited number of samples by 16S rRNA cloning and sequencing. Bacterial genera present at >10(6) CFU/g feces, as determined by quantitative culture, were generally readily detected by T-RFLP, while culture on selective media was more sensitive in detecting facultative anaerobes with lower population counts. In contrast, T-RFLP more readily than culture detected several anaerobic species, also taxa that could not be identified using the database. T-RFLP readily identified bacteria to the genus level and also provided some sub-genus discrimination. Both T-RFLP and culture identified Bifidobacterium, Clostridium and Bacteroides spp. among the most common colonizers of the infantile microbiota throughout the first year of life. T-RFLP analysis showed that microbiota complexity was high in the first weeks of life, declined to a minimum at 1-2 months of age, and thereafter increased again. Principal component analysis revealed that early samples (1 week-6 months) chiefly differed between individual infants, while 12-month samples were similar between children, but different from the early samples. Our results indicate that T-RFLP has high sensitivity and adequate taxonomic discrimination capacity for analysis of gut microbiota composition, but that both culture and molecular based analysis have limitations and both approaches may be needed to obtain a full picture of the complex gut microbiota.
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| 22. |
- Sjöberg, Fei, et al.
(author)
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Elastase as a potential biomarker for radiation-induced gut wall injury of the distal bowel in an experimental mouse model
- 2018
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 57:8, s. 1025-1030
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Journal article (peer-reviewed)abstract
- Background and purpose: Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel.Material and methods: Adult male mice were exposed to two, three, or four fractions of 6Gy or 8Gy irradiation to the sigmoid and rectum of the large bowel, using a linear accelerator. Fecal samples were collected from mice at 1, 3, and 6 weeks post-irradiation. The fecal levels of elastase and calprotectin were analyzed using ELISA.Results: Three and 6 weeks after irradiation, we found a dose-effect relationship between dose of ionizing radiation and the fecal level of elastase; that is significantly higher levels of elastase were observed in mice that had received a high irradiation dose. We also found that irradiated mice hosted in the same cage had a comparable level (either high or low) of elastase. No significant differences were observed from the calprotectin data.Conclusions: We found a clear association between the dose of ionizing radiation to the distal colon and the level of elastase in the fecal samples.
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| 23. |
- Sjöberg, Fei, et al.
(author)
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Low-complexity microbiota in the duodenum of children with newly diagnosed ulcerative colitis
- 2017
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
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Journal article (peer-reviewed)abstract
- Background Inflammatory bowel disease (IBD) is characterized by gut dysbiosis. To date, the large bowel microbiota has been in focus. However, the microbiota of the small intestine may also be of importance, as the small bowel is a site for the induction and control of mucosal immune responses, which can be modulated by constituents of the local microbiota. Duodenal fluids were collected during diagnostic work-up of treatment-naive children who were suspected of having IBD. The duodenal fluids were analyzed by pyrosequencing (average of 32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn's disease (N = 5), and non-IBD controls (N = 8) were compared. Pyrosequencing revealed that the duodenal microbiota of children with ulcerative colitis contained fewer Operational Taxonomic Units (OTUs) per individual than the duodenal microbiota of the controls (P = 0.005). This reduction in richness of the duodenal microbiota was seen for three major phyla: Firmicutes, Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less frequently in the children with ulcerative colitis than in the non-IBD controls, including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P = 0.007), as well as a non-identified member of the order Sphingobacteriales (P = 0.007). In this pilot study, we show that the duodenal microbiota of children with ulcerative colitis exhibits reduced overall richness, despite the fact that the inflammation is primarily localized to the colon. These results should be corroborated in a larger study.
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| 24. |
- Sjöberg, Fei
(author)
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Microbiota of the alimentary tract of children - implications for allergy and inflammatory bowel disease
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Allergy, which is the most common chronic disease in Swedish children and adolescents, is associated with a high standard of living and Western lifestyle. According to the hygiene hypothesis, allergy is due to inadequate stimulation of the immune system by microbes during early childhood, leading to failed maturation of the immune system. The incidences of inflammatory bowel diseases, i.e., ulcerative colitis and Crohn’s disease, have also increased dramatically in Western countries over the last few decades, and currently, these diseases are often diagnosed already in childhood. Epidemiological evidence suggests links between alterations to the intestinal microbiota and these diseases. Thus, studies of the composition of the bacterial microbiota in infants and young children are of relevance for the pathogenesis of both allergic diseases and inflammatory bowel diseases. In this thesis, quantitative culture and DNA-based methods are compared for their abilities to characterize the gut microbiota in infants. Terminal-Restriction Fragment Length Polymorphism (T-RFLP) is based on differences in the 16S rRNA gene sequences between bacteria, as revealed by differences in fragment sizes after restriction enzyme digestion. A database was constructed to identify bacteria based on their fragment sizes. Multi-parallel sequencing of the 16S rRNA gene by pyrosequencing and T-RFLP were compared for sensitivity with quantitative culture of infant fecal samples. Bacterial genera that were present at >106 colony forming units/g feces, as determined by culture, were generally readily detected by DNA-based methods, with the exception of bifidobacteria, which generated only one sequence read per 108 viable bacteria. Clinically and immunologically relevant facultative bacteria, e.g., staphylococci, were often missed by the DNA-based methods due to having low counts in the fecal samples. The studies presented in this thesis indicate that cultivation and molecular-based assays are complementary in generating an overall picture of the complex gut microbiota. In the ALLERGYFLORA cohort study, T-RFLP was used to analyze the salivary microbiota in 4-month-old infants whose parents had the habit of “cleaning” their pacifier by sucking on it, and of control children whose parents did not have this habit. Sharing of the pacifier between parent and infant was associated with reduced risk of the child developing an allergy and altered salivary microbiota in the child. We hypothesize that the oral bacteria transmitted from the parents stimulate the child's immune system in such a way that allergy development is avoided. Samples of the duodenal fluids of children with newly diagnosed and untreated inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and controls (having functional bowel disorders without signs of intestinal inflammation) were analyzed by culture and pyrosequencing. The microbiota of children with ulcerative colitis displayed lower bacterial diversity than that of the control children, and certain bacterial groups were less abundant in the former group. Taken together, the studies presented in this thesis suggest that the compositions of the commensal microbiota in the oral cavity and small intestine affect the risk of developing immunoregulatory diseases, such as allergies and inflammatory bowel diseases.
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| 25. |
- Steineck, Gunnar, 1952, et al.
(author)
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Contouring pudendal nerves.
- 2018
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 57:4, s. 438-439
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Journal article (other academic/artistic)
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| 26. |
- Steineck, Gunnar, 1952, et al.
(author)
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Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Journal article (peer-reviewed)abstract
- © 2017 Steineck et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: During radiotherapy unwanted radiation to normal tissue surrounding the tumor triggers survivorship diseases; we lack a nosology for radiation-induced survivorship diseases that decrease bowel health and we do not know which symptoms are related to which diseases. Methods: Gynecological-cancer survivors were followed-up two to 15 years after having undergone radiotherapy; they reported in a postal questionnaire the frequency of 28 different symptoms related to bowel health. Population-based controls gave the same information. With a modified factor analysis, we determined the optimal number of factors, factor loadings for each symptom, factor-specific factor-loading cutoffs and factor scores. Results: Altogether data from 623 survivors and 344 population-based controls were analyzed. Six factors best explain the correlation structure of the symptoms; for five of these a statistically significant difference (P< 0.001, Mann-Whitney U test) was found between survivors and controls concerning factor score quantiles. Taken together these five factors explain 42 percent of the variance of the symptoms. We interpreted these five factors as radiation-induced syndromes that may reflect distinct survivorship diseases. We obtained the following frequencies, defined as survivors having a factor loading above the 95 percent percentile of the controls, urgency syndrome (190 of 623, 30 percent), leakage syndrome (164 of 623, 26 percent), excessive gas discharge (93 of 623, 15 percent), excessive mucus discharge (102 of 623, 16 percent) and blood discharge (63 of 623, 10 percent). Conclusion: Late effects of radiotherapy include five syndromes affecting bowel health; studying them and identifying the underlying survivorship diseases, instead of the approximately 30 long-term symptoms they produce, will simplify the search for prevention, alleviation and elimination.
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| 27. |
- Steineck, Gunnar, 1952, et al.
(author)
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Late radiation-induced bowel syndromes, tobacco smoking, age at treatment and time since treatment - gynecological cancer survivors
- 2017
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 56:5, s. 682-691
-
Journal article (peer-reviewed)abstract
- Background: It is unknown whether smoking; age at time of radiotherapy or time since radiotherapy influence the intensity of late radiation-induced bowel syndromes.Material and methods: We have previously identified 28 symptoms decreasing bowel health among 623 gynecological-cancer survivors (three to twelve years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five separate late bowel syndromes through factor analysis. Here, we related possible predictors of bowel health to syndrome intensity, by combining factor analysis weights and symptom frequency on a person-incidence scale.Results: A strong (p<.001) association between smoking and radiation-induced urgency syndrome was found with a syndrome intensity (normalized factor score) of 0.4 (never smoker), 1.2 (former smoker) and 2.5 (current smoker). Excessive gas discharge was also related to smoking (p=.001). Younger age at treatment resulted in a higher intensity, except for the leakage syndrome. For the urgency syndrome, intensity decreased with time since treatment.Conclusions: Smoking aggravates the radiation-induced urgency syndrome and excessive gas discharge syndrome. Smoking cessation may promote bowel health among gynecological-cancer survivors. Furthermore, by understanding the mechanism for the decline in urgency-syndrome intensity over time, we may identify new strategies for prevention and alleviation.
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| 28. |
- Steineck, Gunnar, et al.
(author)
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Late radiation-induced bowel syndromes, tobacco smoking, age at treatment and time since treatment–gynecological cancer survivors
- 2017
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In: Acta Oncologica. - 1651-226X .- 0284-186X. ; 56:5, s. 682-691
-
Journal article (peer-reviewed)abstract
- Background: It is unknown whether smoking; age at time of radiotherapy or time since radiotherapy influence the intensity of late radiation-induced bowel syndromes. Material and methods: We have previously identified 28 symptoms decreasing bowel health among 623 gynecological-cancer survivors (three to twelve years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five separate late bowel syndromes through factor analysis. Here, we related possible predictors of bowel health to syndrome intensity, by combining factor analysis weights and symptom frequency on a person-incidence scale. Results: A strong (p
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| 29. |
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| 30. |
- Steineck, Gunnar, 1952, et al.
(author)
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Toward Restored Bowel Health in Rectal Cancer Survivors
- 2016
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In: Seminars in Radiation Oncology. - : Elsevier BV. - 1053-4296 .- 1532-9461. ; 26:3, s. 236-250
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Journal article (peer-reviewed)abstract
- As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors.
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| 31. |
- Voss, Ulrikke, et al.
(author)
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Irradiation Induces Tuft Cell Hyperplasia and Myenteric Neuronal Loss in the Absence of Dietary Fiber in a Mouse Model of Pelvic Radiotherapy
- 2022
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In: Gastroenterology Insights. - : MDPI AG. - 2036-7422. ; 13:1, s. 87-102
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Journal article (peer-reviewed)abstract
- Pelvic radiotherapy is associated with chronic intestinal dysfunction. Dietary approaches, such as fiber enrichment during and after pelvic radiotherapy, have been suggested to prevent or reduce dysfunctions. In the present paper, we aimed to investigate whether a diet rich in fermentable fiber could have a positive effect on radiation-induced intestinal damage, especially focusing on tuft cells and enteric neurons. Male C57BL/6 mice were fed either a purified non-fiber diet or the same purified diet with 5% or 15% oat fiber added, starting two weeks prior to sham-irradiation or irradiation with four fractions of 8 Gray. The animals continued on the diets for 1, 6 or 18 weeks, after which the gross morphology of the colorectum was assessed together with the numbers of enteric neurons, tuft cells and crypt-surface units. The results showed that dietary fiber significantly affected the intestinal morphometrics, both in the short and long-term. The presence of dietary fiber stimulated the re-emergence of crypt-surface unit structures after irradiation. At 18 weeks, the animals fed with the non-fiber diet displayed more myenteric neurons than the animals fed with the dietary fibers, but irradiation resulted in a loss of neurons in the non-fiber fed animals. Irradiation, but not diet, affected the tuft cell numbers, and a significant increase in tuft cells was found 6 and 18 weeks after irradiation. In conclusion, dietary fiber intake has the potential to modify neuronal pathogenesis in the colorectum after irradiation. The long-lasting increase in tuft cells induced by irradiation may reflect an as yet unknown role in the mucosal pathophysiology after pelvic irradiation. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
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