Consumption of Acidic Water Alters the Gut Microbiome and Decreases the Risk of Diabetes in NOD Mice

J Histochem Cytochem. 2014 Apr;62(4):237-50. doi: 10.1369/0022155413519650. Epub 2014 Jan 22.


Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.

Keywords: T-cells; diet; microbiota; mouse model; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroides / isolation & purification
  • CD4-Positive T-Lymphocytes / metabolism
  • Clostridium / isolation & purification
  • DNA, Bacterial / analysis
  • Diabetes Mellitus, Experimental / etiology*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Drinking
  • Feces / microbiology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Fresh Water / chemistry*
  • Gastrointestinal Tract / chemistry
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / microbiology*
  • Hydrogen-Ion Concentration
  • Interleukin-17 / metabolism
  • Lactobacillus / isolation & purification
  • Mice
  • Mice, Inbred NOD


  • DNA, Bacterial
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17