Drinking Acidified Water May Have Beneficial Effects in Children With CLN3, Mouse Study Suggests
The effects of water with higher acid levels are probably linked to changes in the population of microorganisms that live in the digestive tract, called gut microbiota, the researchers said.
The study, “Changes in motor behavior, neuropathology, and gut microbiota of a Batten disease mouse model following administration of acidified drinking water,” was published in Nature Scientific Reports.
Mouse models of CLN3 disease, the pediatric form of the rare neurodegenerative disorder Batten disease, mimic the symptoms found in human patients, such as motor and cognitive decline.
Acidified drinking water has a pH between 2.5 and 3.0, in contrast with a pH of 8.4 found in normal tap water. Researchers often provide acidified drinking water to mice in the laboratory to prevent the spreading of bacterial infections, since many infectious bacteria cannot survive in acidic conditions.
However, recent studies have shown that changes in water acidity disturb the composition of the gut microbiota.
“Accumulated evidence indicates that the gut microbial community can undergo significant changes in neurological and neurodegenerative conditions/diseases, and a complex interaction exists between the central nervous system and gut microbiota,” the researchers said.
This suggests that changes in gut microbiota could impact the symptoms of the CLN3 mouse model, they said.
The team found that, once their lab mouse facility switched to acidified drinking water, Batten mice began to show changes in motor skills. In fact, motor deficits in these mice began disappearing to the extent that these animals preformed similarly to healthy mice in a pole climbing assay.
“This indicated a disease-modifying effect of acidified water, possibly through an influence on the composition of the gut microbiota,” the researchers said.
To further explore this observation, the team compared the effects of water acidity in mice with Batten disease and healthy animals (controls). The mice were given either normal tap water or acidified water from the time of weaning. Their motor and behavioral performance was assessed at 3 and 6 months of age, with 6 months representing the midstage of the disease.
Three-month-old Batten mice who drank the more acidic water had similar motor performance to control animals. However, at six months, the Batten mice presented with motor decline independent of which water they drank.
Drinking acidified water improved the results of behavioral tests and prevented microglial activation — an early marker of nerve cell loss and synonymous with inflammation — in Batten mice at both three and six months of age.
“Altogether, these results suggest that acidified drinking water delays disease progression in [Batten disease] mice,” the researchers said.
The team also noted that, in healthy control mice, drinking acidified water decreased motor performance, impaired spatial orientation — the ability to clearly differentiate between up and down — and increased microglial activation. However, balance and motor coordination in these animals was not affected.
The changes observed as a result of drinking water with higher acid levels were attributed to alterations in the composition of the gut microbiota.
Healthy animals who received acidified water had a significant decrease in the relative abundance of the Lactobacillaceae family, while Batten mice showed more resistance to these alterations. That suggests that “the lack of Cln3 expression in the gastrointestinal tract, particularly in the colon, stabilizes the gut microbiota composition,” the researchers said.
However, in Batten mice, the higher-acid water changed the relative abundance of Turicibacter at three months, and of Lactococcus and Turicibacter at six months.
“In summary, our results in [Batten] mice suggest that acidified drinking water may have beneficial effects for CLN3 Batten disease patients,” the researchers wrote. “The acidified water-induced changes in glial activation, gut microbiota composition, and behavior of [Batten] and wild type mice indicate that the [acidity] of drinking water is an environmental factor that strongly influences the results of [mouse studies],” they added.