Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study

Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. Research design and methods We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Results Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. Conclusions We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.Peer reviewe

Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice

Background: Gastrointestinal complications are the main cause of death in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Available treatments often restore biochemical homeostasis, but fail to cure gastrointestinal symptoms. Methods: We evaluated the small intestine neuromuscular pathology of an untreated MNGIE patient and two recipients of hematopoietic stem cells, focusing on enteric neurons and glia. Additionally, we evaluated the intestinal neuromuscular pathology in a mouse model of MNGIE treated with hematopoietic stem cell gene therapy. Quantification of muscle wall thickness and ganglion cell density was performed blind to the genotype with ImageJ. Significance of differences between groups was determined by two-tailed Mann-Whitney U test (P < 0.05). Results: Our data confirm that MNGIE presents with muscle atrophy and loss of Cajal cells and CD117/c-kit immunoreactivity in the small intestine. We also show that hematopoietic stem cell transplantation does not benefit human intestinal pathology at least on short-term. Conclusions: We suggest that hematopoietic stem cell transplantation may be insufficient to restore intestinal neuropathology, especially at later stages of MNGIE. As interstitial Cajal cells and their networks play a key role in development of gastrointestinal dysmotility, alternative therapeutic approaches taking absence of these cells into account could be required

Ameryka w lustrze biografii wielkich Amerykanów: nieformalny przewodnik dla czytelników

Taking as a starting point the events of Donald Trump’s presidency, the healthcare crisis caused by the outbreak of Covid-19 pandemic, and the perception of the United States of America as a (fading) symbol of democracy, this essay investigates whether a balanced discussion on the contemporary image of America is still possible. As it is argued, such a balanced view might be achieved thanks to the genre of biography. Therefore, a subjective selection of biographies contributing to this view is presented, starting with those dedicated to Alexander Hamilton and George Washington and ending with the ones focusing on Michelle and Barack Obama; as it is shown, they allow us to investigate the complicated personages who contributed to the contemporary image of America.Wychodząc od wydarzeń pierwszej kadencji Donalda Trumpa, kryzysu amerykańskiej opieki zdrowotnej w kontekście pandemii Covid-19 i Stanów Zjednoczonych Ameryki postrzeganych jako (gasnący) symbol demokracji, niniejszy esej stawia pytanie, czy możliwa jest wyważona dyskusja o współczesnym obrazie Ameryki. Zdaniem autora, taki ogląd można wypracować dzięki gatunkowi biografii. Esej, tym samym, przedstawia subiektywny wybór biografii, od Alexandra Hamiltona i George’a Washingtona po Michelle i Baracka Obamów, które pozwalają przyjrzeć się skomplikowanym postaciom, które wpłynęły na kształt Ameryki, jaką znamy dzisiaj