Managing customer relationships in industrial context: customer analysis and strategic customer plan : Case Andritz Pulp and Paper Business Area

Siirretty Doriast

Characterization of Intestinal Microbiota in Healthy Adults and the Effect of Perturbations

The human gastrointestinal microbiota is a complex ecosystem harbouring trillions of bacteria from hundreds of species. Co-evolution has resulted in a mutually beneficial relationship in which gut bacteria make essential contributions to human health, moreover alterations in the microbiota composition and function have been associated to several disease states. In order to identify such changes in patients, it is essential to characterize the microbiota of healthy subjects. In this thesis the intestinal microbiota of healthy adults were thoroughly investigated and shown to display high subject-specificity and stability over time. Moreover, significant correlations between the microbiota and mild intestinal symptoms were identified, including the association of abdominal pain and bloating with the reduction of health-associated bifidobacteria. The intestinal microbiota of healthy subjects was benchmarked against two conditions that were hypothesized to perturb the microbial composition; bowel cleansing, a normal procedure prior colonoscopy and irritable bowel syndrome (IBS), a common disorder estimated to affect 10% of Finnish population. Adequate bowel cleansing by lavage has been shown to be safe for patients, but its long-term effects on the intestinal microbiota, and especially the potential alterations arising from different dosing regimes have not been addressed previously. We showed that there is a short but drastic reduction of the intestinal microbiota after lavage, however the microbiota recovers back to its original form within two weeks after the treatment. Additionally, we found that the recovery rate is dependent on the dosing of the purgative agent, suggesting that two smaller volumes of the purgative should be preferred over a single larger dose. There is growing evidence of the involvement of the intestinal microbiota in the pathophysiology of different IBS subtypes. However, the microbial component in post-infectious IBS patients has previously remained uncharacterised. In parallel to the characterization of intestinal microbiota of PI-IBS patients, the aim of this work was to address the associations between the intestinal microbiota and patient's clinical characteristics. We identified a bacterial signature of 27 taxa and the abundances of implicated bacteria correlated with clinical markers as well as expression levels of several host gene pathways, all suggesting an impaired gut epithelial barrier function in IBS. Observation of these specific associations between the host and intestinal microbiota may provide novel insights into the origin and mechanistic background of intestinal symptoms in IBS as well as enables novel stratification of the IBS patient material with a different aetiology. In summary, this thesis characterised the intestinal microbiota of healthy individuals and showed how perturbations such as IBS and bowel cleansing disrupt the composition, and detected associations between the microbiota and health parameters of the host. The results have clinical relevance by providing novel and a much needed tool for segregating the IBS patient material objectively as well as providing grounds for choosing the split-dosing regime of the purgative agent as an optimal bowel cleansing method. Furthermore, associations between the microbiota and health markers of the host were detected that will give grounds for future research on the aetiology of IBS.Ihmisen suolistomikrobiosto on monimuotoinen ekosysteemi, joka muodostuu triljoonista bakteereista. Ihmisen ja bakteeriston yhteinen evoluutio on johtanut keskinäiseen hyötysuhteeseen, jossa suolistomikrobisto osallistuu ihmisen terveyden ylläpitoon. Muutokset mikrobiston koostumuksessa tai toiminnassa on yhdistetty useisiin tauteihin. Jotta voitaisiin luotettavasti tunnistaa sairauksiin liittyviä mikrobistomuutoksia, on tärkeää tietää millainen on terveen ihmisen suolistomikrobisto. Tässä väitöskirjassa määriteltiin terveiden aikuisten suolistomikrobiston koostumusta ja osoitettiin sen olevan hyvin yksilöllinen ja pysyvän muuttumattomana 7 viikon seurannassa. Tutkitussa aineistossa lievien suolistovaivojen, kuten turvotuksen ja vatsakipujen esiintyvyys oli yhteydessä terveysvaikutteisten bifidobakteerien määrän laskuun. Terveiden aikuisten suolistomikrobistolöydöksiä verrattiin edelleen kahteen suoliston häiriötilaan; suolen tyhjennykseen, joka suoritetaan ennen kolonoskopiaa, sekä ärtyneen suolen oireyhtymään (IBS), josta kärsii noin 10% Suomen väestöstä. Suolen tyhjennys PEG liuoksella on todennetusti potilaalle vaaraton toimenpide, kuitenkaan sen pitkäaikaisvaikutusta tai kahden eri annoskoon merkitystä suolistomikrobistolle ei oltu aikaisemmin tutkittu. Tässä työssä osoitettiin, että suolen tyhjennyksellä on suuri, mutta lyhytaikainen vaikutus mikrobiston koostumukseen. Lähtötilanteen mikrobisto palautui entiselleen 2 viikon kuluessa tyhjennyksestä. Kuitenkin tyhjennysaineen annostus vaikutti mikrobiston palautumiseen; kaksi erillistä annosta aiheutti vähemmän pidempiaikaisia mikrobistomuutoksia kuin yksi suurempi annos. Suolistomikrobistomuutokset on yleisesti yhdistetty ärtyneen suolen oireyhtymään, mutta muutosten luonnetta gastroenteriitin jälkeisessä IBS:ssä ei ole aikaisemmin tutkittu. Taudin oireet vaihtelevat suuresti potilaiden välillä ja yksi tutkimuksen tarkoituksista olikin löytää yhteyksiä potilaiden kliinisen kuvan ja mikrobistomuutosten välillä. Tulokset viittaavat suolistobakteerien muutosten liittyvän suolen limakalvoesteen heikentyneeseen toimintaan. Lisäksi löytyneiden mikrobistomuutosten avulla pystyttiin luokittelemaan potilaat etiologian mukaisesti. Näiden yhteyksien löytyminen auttaa ymmärtämään mikrobiston merkitystä ärtyneen suolen oireyhtymän oireiden synnyssä. Yhteenvetona, tässä väitöskirjatutkimuksessa kuvattiin suolistomikrobiston piirteitä terveissä aikuisissa. Lisäksi selvitettiin kuinka mikrobistoa muokkaavat tekijät, kuten suolen tyhjennys, sekä ärtyneen suolen oireyhtymä muuttavat mikrobiston koostumusta, ja selvitettiin näiden muutosten ja potilaiden terveyttä kuvaavien kliinisten muuttujien välisiä yhteyksiä

Contemporary cabinets of curiosities. Capturing environment and experiences into digital collections.

This thesis looks into the phenomenon of capturing environment and experiences into digital collections. Digital collecting can be seen as a cross-section of today’s situation where physical and digital are intertwined and where the fast life pace makes many people capture the current moments to be remembered later. With digital equipment it’s more possible to collect things in various ways and also to describe unseen things such as memories, smells and feelings. Many things that we used to have as concrete, tangible objects have become digital. For example a butterfly collection can be done without taking the lives of butterflies but instead by capturing virtual butterflies or displaying representations of them online. Collecting is a multidimensional activity and there is a fine line between collecting and hoarding, for instance. Collecting has a long tradition and now it has stepped into an era where it gets new forms by using new media possibilities such as digital devices, applications, platforms and social communities. In this thesis I am exploring the individual level collecting done by today’s capturing possibilities, especially turning the physical environment and experiences into digital forms. I am using my own digital photography collections and other cases as examples along with the related literature and a survey I implemented. After realizing that I had collections in the first place, I wanted to know why I had been creating them and what digital collecting was about. That was the starting point for this thesis topic. My research questions are: What is digital collecting about? Why people digitally collect things? According to my research, digitally collecting one’s environment and experiences relates to wide range of phenomena such as self-expression, comprehension and memory. Digital collections reflect collector’s thinking and identity and the contemporary culture. The results suggest that the motives for digitally collecting derive more from the collector’s inner life than from the actual things collected. The findings help to understand better the contemporary collecting and its links to our modern lives and it also offers viewpoints for further research

The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

The intestinal microbiota, composed of pro- and anti-inflammatory microbes, has an essential role in maintaining gut homeostasis and functionality. An overly hygienic lifestyle, consumption of processed and fiber-poor foods, or antibiotics are major factors modulating the microbiota and possibly leading to longstanding dysbiosis. Dysbiotic microbiota is characterized to have altered composition, reduced diversity and stability, as well as increased levels of lipopolysaccharide-containing, proinflammatory bacteria. Specific commensal species as novel probiotics, so-called next-generation probiotics, could restore the intestinal health by means of attenuating inflammation and strengthening the epithelial barrier. In this review we summarize the latest findings considering the beneficial effects of the promising commensals across all major intestinal phyla. These include the already well-known bifidobacteria, which use extracellular structures or secreted substances to promote intestinal health. Faecalibacterium prausnitzii, Roseburia intestinalis, and Eubacterium hallii metabolize dietary fibers as major short-chain fatty acid producers providing energy sources for enterocytes and achieving anti-inflammatory effects in the gut. Akkermansia muciniphila exerts beneficial action in metabolic diseases and fortifies the barrier function. The health-promoting effects of Bacteroides species are relatively recently discovered with the findings of excreted immunomodulatory molecules. These promising, unconventional probiotics could be a part of biotherapeutic strategies in the future.Peer reviewe

Fecal Transplantation Treatment of Antibiotic-Induced, Noninfectious Colitis and Long-Term Microbiota Follow-Up

Peer reviewe

Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC

Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC

The composition of the perinatal intestinal microbiota in horse

The establishment of the intestinal microbiota is critical for the digestive and immune systems. We studied the early development of the rectal microbiota in horse, a hindgut fermenter, from birth until 7 days of age, by qPCR and 16S rRNA gene amplicon sequencing. To evaluate initial sources of the foal microbiota, we characterised dam fecal, vaginal and oral microbiotas. We utilised an amplicon sequence variant (ASV) pipeline to maximise resolution and reproducibility. Stringent ASV filtering based on prevalence and abundance in samples and controls purged contaminants while preserving intestinal taxa. Sampled within 20 minutes after birth, rectal meconium contained small amounts of diverse bacterial DNA, with a profile closer to mare feces than mouth. 24 hours after birth, rectum was colonised by Firmicutes and Proteobacteria, some foals dominated by single genera. At day 7, the rectal genera were still different from adult feces. The mare vaginal microbiota contributed to 24 h and 7 day microbiotas. It contained few lactobacilli, with Corynebacterium, Porphyromonas, Campylobacter and Helcococcus as the most abundant genera. In the oral mucosa, Gemella was extremely abundant. Our observations indicate that bacteria or bacterial components are present in the intestine immediately after birth, but the newborn microbiota changes rapidly.Peer reviewe