Gut Microbiomes Permanently Altered in Mice When Nursing Moms are Fed a Low-Fiber Diet

A new study has found that mice whose mothers were fed a low-fiber diet while nursing have a permanently altered microbiome, low-level gut inflammation and are more prone to obesity. The study is published in Cell Host & Microbe.

Inheriting your microbiome

The gut microbiome is the community of micro-organisms including bacteria, viruses and fungi that are resident in our gut. These contribute to protecting and supporting the epithelial cells which line the intestine and help to produce metabolites and nutrients – for example, the enzymes required to produce vitamin B12 can only be found in bacteria. As a result, the status and “health” of our microbiome can in turn have a profound influence on our own health. Imbalances in our gut microbiome (known as dysbiosis) are associated with a range of conditions including type 2 diabetes, inflammatory bowel disease and obesity.

Our microbiome can, to a degree, change with diet, medication and exposure to environmental factors. Diets high in fiber can affect the diversity and quantity of microbes in our gut, as bacteria ferment indigestible dietary fiber and alter the gut’s pH to prevent colonization by pathogens.

As the knowledge of our microbiome increases, mounting evidence shows that a large part of our gut microbiome is passed down from mother to baby during birth and while breastfeeding. In fact, delivery by Cesarean section can limit the development of the infant’s microbiome, showing how these early events can help to shape our microbiomes for the rest of our lives.

Researchers in the current study were interested in exploring how diet not only influences an individual’s gut microbiome and metabolism, but also that of their offspring, and whether this could dictate their susceptibility to associated conditions like obesity.

Can low-fiber impact offspring?

The researchers studied the impact of a low-fiber maternal diet during nursing. This is due to the role of diet and nursing in maintaining and establishing the gut microbiome, with the researchers hypothesizing that a low-fiber diet would permanently and adversely alter the offspring’s microbiome.

Lactating mouse mothers (dams) were given a low-fiber diet or the research-standard grain-based rodent chow (GBC) until the pups were weaned at three weeks of age, when their feces and microbiomes were analyzed. The findings indicated that dysbiosis caused by the low-fiber diet was transmitted from the dam to the pups. For example, the number of Proteobacteria (described below) was increased in both dams and pups, although to a lesser extent in the pups.

Mice with mothers on the low-fiber diet also had a higher body weight, elevated non-fasting glucose levels and indicators of low-level intestinal inflammation compared to mice with GBC-fed mothers. “I was shocked at how quickly the mice gained weight when they were exposed to this diet,” explained Andrew Gewirtz, senior author of the paper and professor in the Center for Inflammation, Immunity and Infection at Georgia State University. “The data was striking, and I didn’t believe it at first. It took many replications to convince me,” he adds.

However, placing these mice onto GBC after weaning was not sufficient to restore their microbiome. Striking differences (particularly in the abundance of Proteobacteria) remained between microbiomes in mice whose mothers were fed GBC and those whose mothers were fed a low-fiber diet while nursing.

The mice whose mothers were fed the low-fiber diet while nursing had a higher bodyweight than their peers with GBC-fed mothers – however, they gradually lost their elevated bodyweight over several weeks once weaned onto GBC. Nevertheless, the low-fiber maternal diet had left a lasting impression. When these mice were then transferred onto a low-fiber, high-fat diet designed to model diet-induced obesity (DIO) for four weeks, they rapidly gained weight compared to mice with GBC-fed mothers, in addition to increased fat mass and indicators of high blood cholesterol and insulin resistance.

The findings suggest that a low-fiber diet allows the number of Proteobacteria, who do not rely on fiber for nourishment, to increase. Gewirtz adds, “Having high levels of proteobacteria predisposes to an array of diseases including obesity.”

Early life events may shape our future health

Overall, the study showed that a low-fiber maternal diet led to the offspring becoming prone to diet-induced obesity. Gewirtz expanded on what measures may be able to limit this effect: “Introduction of the missing microbes at a young age may correct the problems of maternal fiber deprivation,” he explains, though this requires further study.

“I hope this work can shed light onto how complex our metabolism and microbiome really are and how our early life experiences can shape us for the rest of our lives,” said Gewirtz in a press release.

Reference: Zou J, Ngo VL, Wang Y, Wang Y, Gewirtz AT. Maternal fiber deprivation alters microbiota in offspring, resulting in low-grade inflammation and predisposition to obesity. Cell Host & Microbe. 2022;31(1):1–13. doi: 10.1016/j.chom.2022.10.014 

Prof. Andrew Gewirtz was speaking to Sarah Whelan, Science Writer for Technology Networks.