Fermentable fibres condition colon microbiota and promote diabetogenesis in NOD mice.

AIMS/HYPOTHESIS: Gut microbiota (GM) and diet both appear to be important in the pathogenesis of type 1 diabetes. Fermentable fibres (FFs), of which there is an ample supply in natural, diabetes-promoting diets, are used by GM as a source of energy. Our aim was to determine whether FFs modify GM and diabetes incidence in the NOD mouse. METHODS: Female NOD mice were weaned to a semisynthetic diet and the effects of FF supplementation on diabetes incidence and insulitis were evaluated. Real-time quantitative PCR was employed to determine the effects imposed to gene transcripts in the colon and lymph nodes. Changes to GM were analysed by next-generation sequencing. RESULTS: NOD mice fed semisynthetic diets free from FFs were largely protected from diabetes while semisynthetic diets supplemented with the FFs pectin and xylan (PX) resulted in higher diabetes incidence. Semisynthetic diet free from FFs altered GM composition significantly; addition of PX changed the composition of the GM towards that found in natural-diet-fed mice and increased production of FF-derived short-chain fatty acid metabolites in the colon. The highly diabetogenic natural diet was associated with expression of proinflammatory and stress-related genes in the colon, while the semisynthetic diet free from FFs promoted Il4, Il22, Tgfß and Foxp3 transcripts in the colon and/or pancreatic lymph node. PX in the same diet counteracted these effects and promoted stress-related IL-18 activation in gut epithelial cells. 16S RNA sequencing revealed each diet to give rise to its particular GM composition, with different Firmicutes to Bacteroidetes ratios, and enrichment of mucin-degrading Ruminococcaceae following diabetes-protective FF-free diet. CONCLUSIONS/INTERPRETATION: FFs condition microbiota, affect colon homeostasis and are important components of natural, diabetes-promoting diets in NOD mice.

Causes of Stillbirth in Turku, Finland, 2001-2011.

The objective of the study was to examine the causes of stillbirth in the district of Southwest Finland and to assess the importance of postmortem examination and the selection of a suitable classification system for classifying stillbirths. This study is a cohort study where the fetal autopsies were performed in the Department of Pathology at Turku University Hospital, Finland, 2001-2011. Stillbirths from singleton pregnancies at the gestational age of ≥ 24 + 0 weeks (if unknown, gestational weight ≥ 500 g) (n = 98) were selected. In addition, stillbirths from multiple gestations (n = 6) were also analyzed. The causes of stillbirths were classified according to the Relevant Condition at Death classification system. Maternal risk factors and the role of fetal gestational age and weight for the causes of stillbirth were assessed. The most common causes of singleton stillbirth were lethal congenital anomalies, placental insufficiencies, and constricting loops and knots of the umbilical cord. The cause of singleton stillbirth could be determined for 78% of the cases, leaving 22% unclassified. There were no significant differences in the causes of stillbirth by gestational age or weight. Smoking may increase the incidence of placental abruption ( P < 0.01). The most common causes of stillbirth in Turku, Finland, are consistent with findings from other high-income countries. With careful postmortem examination and ancillary studies, it is possible to find the cause of stillbirth for most of the cases. Even if the stillbirth is left unexplained, many other harmful conditions can be excluded thus benefiting both the parents and the health care unit.