Fiber intake during pregnancy prevents obesity in offspring mice.
Short-chain fatty acids normalize metabolism.


【Introduction】
Increased use of antibiotics, high-calorie diets, and diets low in fiber can cause abnormalities in the intestinal environment, leading to obesity and diabetes. There have been various reports on the effects of such an intestinal environment after birth. On the other hand, although there is the "DOHaD hypothesis" that health and nutritional status during the fetal period and early postnatal period strongly influence future health status, few reports on the fetal period.

In the present study, we conducted a detailed investigation of the effects of the maternal gut environment on fetal development and postnatal disease risk using mice.

【Materials and Results】
<Test 1> Effects of regular and sterile environments on offspring mice
Pregnant mice intestinal were raised on a normal diet in a regular or germ-free environment. The offspring mice were removed by cesarean section on day 18.5 of gestation and were raised by their temporary parents in a typical environment to maintain the same growth environment. After weaning, the mice were fed a high-fat diet, weighed, and subjected to various biochemical analyses. The amount of short-chain fatty acids in the offspring mice's blood and the expression of GPR41 and GPR43, receptors for short-chain fatty acids, in the sympathetic nervous system, intestine, and pancreas were also examined.

Pregnant mice raised under germ-free conditions (germ-free mother mice) became severely obese and showed symptoms of metabolic syndrome such as hyperglycemia and dyslipidemia compared to pregnant mice raised under normal conditions (normal mother mice). There was a significant difference in body temperature, heart rate, energy metabolism, and gastrointestinal hormone PYY and GLP-1 levels in germ-free compared to normal mother mice. The amount of short-chain fatty acids in their blood was also significantly lower.

Although the offspring mice did not have intestinal bacteria and could not produce many short-chain fatty acids, GPR41 and GPR43 were highly expressed in the offspring mice's sympathetic nerves, intestine, and pancreas.

<Test 2> Intervention with and without dietary fiber in a typical intestinal environment
The same study as in Test 1 was conducted on pregnant mice raised on a diet containing little or no dietary fiber or a diet containing 10% dietary fiber (inulin, a polysaccharide) under normal conditions (low and high dietary fiber offspring mice, respectively).

The various measurements for the low dietary fiber offspring mice were the same as for the germ-free offspring mice in Study 1. On the other hand, the high dietary fiber offspring mice significantly suppressed the increase in body weight, blood glucose, and serum lipid levels, and decreased body temperature and heart rate, which were observed in the low dietary fiber offspring mice. The amount of short-chain fatty acids in the blood was also significantly higher.

We conducted a similar study using offspring of pregnant mice raised on a diet containing little dietary fiber and 5% propionic acid, a type of short-chain fatty acid and found that the obesity and obesity-related measurements were seen in the low-fiber offspring were suppressed.

【Discussion and Conclusion】
This study indicated that some of the short-chain fatty acids produced by the intestinal bacteria of pregnant mice reach the offspring via the bloodstream and regulate energy metabolism during growth and prevent obesity in the offspring via GPR41 and GPR43 in the fetuses. The intestinal environments of the mother during pregnancy may influence the formation of the metabolic system of their offspring.

【Research institution】
Tokyo University of Agriculture and Technology (Japan)
Keio University (Japan)

Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice
Science 367, 6481, eaaw8429, 2020