Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.

Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.

Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model.

Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-treatment significantly altered intestinal metabolite levels. Fasting hyperglycemia was associated with the increase in the levels of gluconeogenesis-related enzymes and metabolites without changes in the expression of proinflammatory cytokines and insulin resistance. Oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.

A high-fiber, low-fat diet improves periodontal disease markers in high-risk subjects: a pilot study.

Periodontal disease is related to aging, smoking habits, diabetes mellitus, and systemic inflammation. However, there remains limited evidence about causality from intervention studies. An effective diet for prevention of periodontal disease has not been well established. The current study was an intervention study examining the effects of a high-fiber, low-fat diet on periodontal disease markers in high-risk subjects. Forty-seven volunteers were interviewed for recruitment into the study. Twenty-one volunteers with a body mass index of at least 25.0 kg/m(2) or with impaired glucose tolerance were enrolled in the study. After a 2- to 3-week run-in period, subjects were provided with a test meal consisting of high fiber and low fat (30 kcal/kg of ideal body weight) 3 times a day for 8 weeks and followed by a regular diet for 24 weeks. Four hundred twenty-five teeth from 17 subjects were analyzed. Periodontal disease markers assessed as probing depth (2.28 vs 2.21 vs 2.13 mm; P < .0001), clinical attachment loss (6.11 vs 6.06 vs 5.98 mm; P < .0001), and bleeding on probing (16.2 vs 13.2 vs 14.6 %; P = .005) showed significant reductions after the test-meal period, and these improvements persisted until the follow-up period. Body weight (P < .0001), HbA1c (P < .0001), and high-sensitivity C-reactive protein (P = .038) levels showed improvement after the test-meal period; they returned to baseline levels after the follow-up period. In conclusion, treatment with a high-fiber, low-fat diet for 8 weeks effectively improved periodontal disease markers as well as metabolic profiles, at least in part, by effects other than the reduction of total energy intake.