Voiko laktoosi-intolerantikko sietää laktoosia?

Peer reviewe

Ulosteensiirron nykysuositukset ja uudet sovellukset

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Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications : A case series

Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli (E. coli) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.Peer reviewe

Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients with Obesity Undergoing Bariatric Surgery : A Randomized Clinical Trial

Publisher Copyright: © 2022 Authors. All rights reserved.Importance: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor. Objective: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery. Design, Setting, and Participants: This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022. Interventions: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) Main Outcomes and Measures: The main outcome was weight reduction measured as the percentage of total weight loss (TWL). Results: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P <.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P =.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P <.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P <.001) in the placebo group; however, no difference was observed between the groups. Conclusions and Relevance: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT03391817.Peer reviewe

Kuvantamislöydöksenä koliitti

Vertaisarvioitu.Koliittiin viittaava paksusuolen seinämän turpeus tai poikkeava ulkonäkö vatsan tietokonetomografiassa (TT) on yleinen mutta epäspesifinen löydös. Sen taustalla voi olla useita eri syitä, esimerkiksi tulehduksellinen suolistosairaus, iskemia, infektiotauti, yleissairaus tai jokin suolistosyöpä. Löydös voi olla myös kliinisesti merkityksetön ja liittyä suolen normaaliin toimintaan. Jatkotutkimukset suhteutetaan kliiniseen tilanteeseen. Epäiltäessä infektiotautia otetaan ulosteen mikrobinäytteet. Usein syyn selvittäminen edellyttää kolonoskopiaa

Kuvantamislöydöksenä koliitti

Koliittiin viittaava paksusuolen seinämän turpeus tai poikkeava ulkonäkö vatsan tietokonetomografiassa (TT) on yleinen mutta epäspesifinen löydös. Sen taustalla voi olla useita eri syitä, esimerkiksi tulehduksellinen suolistosairaus, iskemia, infektiotauti, yleissairaus tai jokin suolistosyöpä. Löydös voi olla myös kliinisesti merkityksetön ja liittyä suolen normaaliin toimintaan. Jatkotutkimukset suhteutetaan kliiniseen tilanteeseen. Epäiltäessä infektiotautia otetaan ulosteen mikrobinäytteet. Usein syyn selvittäminen edellyttää kolonoskopiaa.publishedVersio

A distinctive DNA methylation pattern in insufficient sleep

Short sleep duration or insomnia may lead to an increased risk of various psychiatric and cardio-metabolic conditions. Since DNA methylation plays a critical role in the regulation of gene expression, studies of differentially methylated positions (DMPs) might be valuable for understanding the mechanisms underlying insomnia. We performed a cross-sectional genome-wide analysis of DNA methylation in relation to self-reported insufficient sleep in individuals from a community-based sample (79 men, aged 39.3 +/- 7.3), and in relation to shift work disorder in an occupational cohort (26 men, aged 44.9 +/- 9.0). The analysis of DNA methylation data revealed that genes corresponding to selected DMPs form a distinctive pathway: "Nervous System Development" (FDR P value <0.05). We found that 78% of the DMPs were hypomethylated in cases in both cohorts, suggesting that insufficient sleep may be associated with loss of DNA methylation. A karyoplot revealed clusters of DMPs at various chromosomal regions, including 12 DMPs on chromosome 17, previously associated with Smith-Magenis syndrome, a rare condition comprising disturbed sleep and inverse circadian rhythm. Our findings give novel insights into the DNA methylation patterns associated with sleep loss, possibly modifying processes related to neuroplasticity and neurodegeneration. Future prospective studies are needed to confirm the observed associations.Peer reviewe

Fecal microbiota transplantation

ABSTRACT Background The impact of gut microbiota on human health has captivated lay people as well as researchers. The development of modern sequencing methods and their applications in microbiota research have promoted the discovery of complex microbiota communities in the human host. Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile enteritis, and it has also been investigated for many other gut dysbiosis-related conditions. Aims The aim of this dissertation is to investigate the efficacy of FMT in three different diseases and explore the potential of FMT in different clinical settings. Patients and methods This dissertation is built on four studies. The first (I) is a retrospective case series presenting patients treated with FMT and having significant comorbidities or patients who have been treated for conditions other than Clostridioides difficile. The three subsequent studies (II–IV) are randomized controlled trials, in which FMT or placebo was given once by colonoscopy (II–III) or by gastroscopy (IV) for the treatment of irritable bowel syndrome (IBS) (II), for the maintenance of remission in patients with ulcerative colitis (III) or for obesity (IV). Additionally, obesity surgery was performed for patients with obesity half a year after FMT. Microbiota analysis was conducted on the subjects participating in the IBS trial before the FMT treatment and in different time points during the 18-month follow-up. Results Fecal microbiota transplantation cured recurrent Clostridioides difficile enteritis in 11/13 patients with significant comorbidities. Other antibiotic-resistant bacteria, ESBL Escherichia coli and antibiotic-resistant Salmonella, were successfully eradicated from three patients. FMT slightly and transiently reduced irritable bowel symptoms 12 weeks after the treatment compared to the baseline, but there was no statistically significant difference between the treatment group and the placebo at the 12-week time point. However, the microbiota was changed to resemble that of the fecal donor. No advantage of FMT was found in ulcerative colitis or obesity patients compared to the placebo. Conclusions FMT is effective and safe for the treatment of recurrent Clostridioides difficile enteritis for patients with significant comorbidities. The FMT treatment regimens that were used in the clinical trials for IBS, quiescent ulcerative colitis and obesity were safe but ineffective for the treatment of these conditions. Nevertheless, FMT studies for indications beyond Clostridioides difficile enteritis should be continued. New research settings and developing methods for analyzing the microbiota continue to expand our knowledge on microbiota-host interactions and will likely lead toward improvements to FMT protocols and donor selection criteria, which may eventually facilitate the use of FMT or other bacteriotherapies in the treatment of new indications.TIIVISTELMÄ Tausta Suoliston mikrobiston moninaiset vaikutukset ihmisen terveydelle ovat suuren kiinnostuksen ja lisääntyvän tutkimuksen kohde. Geenien sekvensointiin perustuvien tutkimusmenetelmien kehittyminen ja käyttö mikrobiston tutkimuksessa ovat edistäneet suoliston mikrobiston ja ihmisen välisten vuorovaikutusten selvittämistä. Ulosteensiirto on tehokkaaksi todettu ja yleisesti hyväksytty hoitomuoto toistuvan Clostridioides difficile infektion hoitoon. Ulosteensiirtoa tutkitaan monien muiden suoliston mikrobiston epätasapainoon liitettyjen sairauksien hoitoon. Tavoitteet Väitöskirjan tavoitteena on selvittää ulosteensiirron tehoa kolmen eri sairauden hoidossa ja tutkia ulosteensiirron potentiaalia erilaisissa kliinisissä tilanteissa. Potilaat ja menetelmät Väitöskirja perustuu neljään osatyöhön, joista ensimmäisessä (I) kerättiin ulosteensiirrolla hoidettuja potilaita, joilla oli jokin immuniteettia alentava perussairaus sekä sellaisia potilaita, joita oli hoidettu jonkin muun syyn kuin toistuvan Clostridioides difficile infektion vuoksi. Kolme jälkimmäistä osatyötä (II-IV) olivat satunnaistettuja lumekontrolloituja tutkimuksia, joissa potilaille annettiin tähystimen kautta ulosteensiirre tai omasta ulosteesta valmistettu lumesiirre joko paksusuolen tähystyksessä (II-III) tai mahalaukun tähystyksessä (IV) joko ärtyvän suolen oireyhtymän hoitoon (II), haavaisen paksusuolitulehduksen rauhallisen vaiheen, remission, ylläpitoon (III) tai lihavuuden hoitoon (IV). Lihavuudesta kärsiville potilaille tehtiin lisäksi lihavuusleikkaus puoli vuotta ulosteensiirron jälkeen. Ärtyvän suolen oireyhtymästä kärsiville potilaille tehtiin mikrobistoanalyysi ennen hoitoa ja sen jälkeen. Tulokset Ulosteensiirto paransi toistuvan Clostridioides difficile suolitulehduksen 11/13 potilaalta, joilla oli vaikea liitännäissairaus. Kolmella potilaalla antibiooteille vastustuskykyisten bakteerien, ESBL Escherichia colin ja antibioottiresistentin Salmonellan, häätäminen suolistosta onnistui ulosteensiirrolla. Ärtyvän suolen oireyhtymässä todettiin lievää ohimenevää oireiden vähenemistä ulosteensiirron jälkeen, muttei tilastollisesti merkitsevää eroa lumeryhmään verrattuna. Suoliston mikrobisto kuitenkin muuttui samankaltaiseksi kuin ulosteenluovuttajalla. Haavaista paksusuolitulehdusta sairastavilla potilailla ulosteensiirrosta ei ollut apua remission ylläpidossa lumeeseen verrattuna, eikä myöskään lihavuuden hoidossa ulosteensiirto ollut annettua lumehoitoa tehokkaampi. Päätelmät Ulosteensiirto on tehokas ja turvallinen hoitomuoto toistuvan Clostridioides difficile infektion hoitoon myös potilailla, joilla on muu vaikea sairaus. Ulosteensiirto kontrolloiduissa tutkimuksissa käyttämällämme menetelmällä ei ollut tehokas ärtyvän suolen oireyhtymän, haavaisen koliitin remission ylläpidon tai lihavuuden hoidossa. Näissä ja monissa muissa tautityhmissä ulosteensiirtoa kannattaa kuitenkin edelleen tutkia. Kehittyvät tutkimusasetelmat ja mikrobiston tutkimusmenetelmät tuovat lisätietoa mikrobiston ja terveyden yhteyksistä ja edesauttavat ulosteensiirtohoidon kehittämistä esimerkiksi luovuttajien valinnan osalta, ja todennäköisesti johtavat lopulta ulosteensiirron tai siitä edelleen kehitettyjen mikrobiterapioiden käyttöönottoon myös uusissa tautiryhmissä

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