Diabetic cats have decreased gut microbial diversity and a lack of butyrate producing bacteria

none11noneKieler, Ida Nordang*; Osto, Melania; Hugentobler, Leoni; Puetz, Lara; Gilbert, M. Thomas P.; Hansen, Torben; Pedersen, Oluf; Reusch, Claudia E.; Zini, Eric; Lutz, Thomas A.; Bjørnvad, Charlotte ReinhardKieler, Ida Nordang; Osto, Melania; Hugentobler, Leoni; Puetz, Lara; Gilbert, M. Thomas P.; Hansen, Torben; Pedersen, Oluf; Reusch, Claudia E.; Zini, Eric; Lutz, Thomas A.; Bjørnvad, Charlotte Reinhar

Human-derived antibody targeting pancreatic islet amyloid for the treatment of type 2 diabetes

Typ 2 Diabetes (T2DM) ist weltweit eine der häufigsten Erkrankungen des Menschen. Ein typisches Merkmal des T2DM sind Amyloid Ablagerungen im Pankreas, die aus dem sog. "Islet Amyloid Polypeptide" (IAPP) bestehen und deren Bildung stufenweise über die Aggregation von IAPP Monomeren zu Oligomeren und Fibrillen abläuft. Toxische IAPP Oligomere sind wahrscheinlich für Funktionsstörungen der β-Zellen und letztlich deren Zelltod verantwortlich. Keine der momentan verfügbaren T2DM-Behandlungen richtet sich gegen die Aggregation von IAPP. Ein Antikörper (NI-203.26C11), welcher humane IAPP Aggregate bindet, wurde in vitro und in vivoidentifiziert, geklont und charakterisiert. Da IAPP von Ratten nicht amyloidogen ist, wurden transgene Ratten verwendet, die das humane IAPP Gen (hIAPP, RIPHAT Ratten) exprimieren. NI-203.26C11 verbesserte die Glukose Toleranz sowie die β-Zell Funktion, erhöhte die Insulin Sekretion, reduzierte die Nüchternglukose und normalisierte die Gewichtszunahme bei den RIPHAT Ratten im Vergleich zu Kontrolltieren. In einer Dosis-Wirkungs-Studie wurden die drei getesteten Dosierungen (1, 3, 10 mg/kg) als sicher und wirksam eingestuft. Interessanterweise zeigten 1 mg/kg und 10 mg/kg eine bessere Wirkung als 3 mg/kg bezüglich der Glukose Toleranz und der Erhöhung der Insulin Sekretion. Die tiefere Dosierung normalisierte sogar die Gewichtszunahme. Folglich stellt die passive Immunisierung eine vielversprechende Strategie in der Behandlung von T2DM dar. Type 2 diabetes (T2DM) is one of the most important public health challenges in humans. One of the hallmarks of T2DM is the deposition of islet amyloid derived from islet amyloid polypeptide (IAPP) in pancreatic islets. Amyloidogenesis involves the stepwise aggregation of IAPP monomers into oligomers, fibrils and, ultimately, mature amyloid deposits. The small toxic IAPP oligomers seem to cause β-cell failure and death. None of the available treatments against T2DM counteracts the aggregation of IAPP and the subsequent loss of pancreatic β-cells. A human-derived antibody NI-203.26C11, which targets human IAPP aggregates was identified, cloned and characterized in vitroand in vivo. Because rat IAPP is not amyloidogenic, transgenic rats with the human IAPP gene (hIAPP, RIPHAT rats) were used. NI-203.26C11 significantly improved glucose tolerance and β-cell function, increased insulin secretion and pancreatic insulin content, reduced fasting glucose and normalized body weight in NI-203.26C11-treated RIPHAT rats compared to controls. In a dose-response study, three different doses of NI-203.26C11 (1, 3, 10 mg/kg) were found to be safe and effective in slowing the progression of T2DM. Interestingly, 1 mg/kg and 10 mg/kg were generally more effective than 3 mg/kg in improving glucose tolerance and insulin secretion. The lower dose even normalized body weight gain. As conclusion, passive immunization targeting IAPP aggregates is a very promising approach to treat T2DM

Dog feeding practices and supplement use with regard to exercise routine in Switzerland – a survey

INTRODUCTION: Regular exercise is related to owner awareness of their dog’s body condition and feeding habits [1]. We hypothesized that owners seem to overestimate the impact of their dog’s working regimen on its energy and nutritional requirements. The goal of this survey was to explore dog owners’ feeding habits depending on sport/ working intensity (WI) of their dogs. Animals, materials and methods: This survey was conducted at an annual dog exhibition in Switzerland. A set of 14 questions were asked: 4 about the dog, 3 about the WI routine and 7 about feeding routine and supplement use. 247 owners completed the survey. The obtained data were descriptively evaluated using Microsoft Excel (Excel 365, NM, USA). Data regarding feeding habits were evaluated with respect to work use (C group = no work, W group = work or sport use). Text answers regarding the category of W for which the dog was used were categorized in 13 different categories. RESULTS AND DISCUSSION: Characteristics of the study population are displayed in Table 1. Overall, 57% of the dogs were classified in the W group of which agility (n = 29), companion/ guard dog training (n = 28), and mantrailing (n = 20) were the most common. 36% of dogs in the W group were used twice per week, 28% once per week and 26% 3 to 4 times per week for W. Most activities of W dogs lasted for 1-2 h (38% of W dogs), followed by activities lasting for 30 min to 1 hour (34% of W dogs) and activities shorter than 30 min (18% of W dogs). In W dogs, 54% of the owners believed that their dog does not have additional nutritional needs due to WI while 29% believed that their dog has additional nutritional needs due to WI. Feeding preferences were dry food (52% of W, 49% of C), wet food (25% of W, 27% of C), and BARF in the W group (13%) and home cooked in the C group (14%). Regardless of WI, dog owners found a protein rich diet important (58 and 57% in W and C, respectively). Most owners thought that the nutritional needs of their dog can be met with a diet with few components (58% in W, 63% in C group) while 23 and 21% in the W and C group thought that a large variety of foods is necessary to cover the nutritional needs of their dog. Most participants rated the use of supplements to the diet as necessary depending on the diet (36% in W group, 26% in C group). The use of supplements was rated as “always healthy but not necessary” by 25% in the W and 21% in the C group. The most used supplements in the W group were oils (23%), green-lipped mussel products (13%) and vitamin and mineral supplements (12%). In the C group oils (26%), vitamin and mineral supplements (11%) and green-lipped mussel products (9%) were the most used. 11% of the W group and 19% of the C group did not report any supplement use. CONCLUSION: In conclusion, this survey suggests that feeding habits of dog owners mainly differ regarding the use of supplements. Further studies therefore should investigate the quantitative impact of the supplements on dietary nutrient compositio

Diabetic cats have decreased gut microbial diversity and a lack of butyrate producing bacteria

Obesity and inactivity are major risk factors of feline diabetes mellitus (FDM) and human type II diabetes mellitus (T2DM). In recent years, changes in the gut microbiota have been suggested as a contributing factor to T2DM. Whether the gut microbiota (GM) composition plays a role in FDM remains unknown. The aim of the current study was firstly a cross-sectional comparison of the GM of diabetic cats, to that of lean, and of obese/overweight non-diabetic cats of a similar age. Specifically, fecal samples from 82 privately-owned cats from Denmark and Switzerland were sequenced using 16S rRNA gene amplicon metabarcoding. Secondly dietary intervention data was generated, by obtaining additional samples from a subset of cats after placing them on a high-protein diet for four weeks. The GM diversity of diabetic cats was lower than that of lean cats in the cross-sectional study, and lower compared to lean and to overweight/obese cats after diet intervention. Diabetic cats also exhibited fewer Anaerotruncus, Dialister, and unknown Ruminococcaceae than lean cats. Serum fructosamine levels correlated negatively with Prevotellaceae abundance and positively with Enterobacteriaceae abundance. In summary the intestinal microbiota of diabetic cats was characterized by decreased GM diversity and loss of butyrate producing bacterial genera