Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats

Abstract

A maternal high‐fat/sucrose diet, in the presence of maternal obesity, can program increased susceptibility to obesity and metabolic disease in offspring. In particular, nonalcoholic fatty liver disease risk is associated with poor maternal nutrition and obesity status, which may manifest via alterations in gut microbiota. Here, we report that in a preclinical model of diet‐induced maternal obesity, maternal supplementation of a high‐fat/sucrose diet with the prebiotic oligofructose improves glucose tolerance, insulin sensitivity, and hepatic steatosis in offspring following a long‐term high‐fat/sucrose dietary challenge compared with offspring of untreated dams. These improvements are associated with alterations in gut microbial composition and serum inflammatory profiles in early life and improvements in inflammatory and fatty‐acid gene expression profiles in tissues. Serum metabolomics analysis highlights potential metabolic links between the gut microbiota and the degree of steatosis, including alterations in 1‐carbon metabolism. Overall, our data suggest that maternal prebiotic intake protects offspring against hepatic steatosis and insulin resistance following 21 wk of high fat/sucrose diet, which is in part due to alterations in gut microbiota.—Paul, H. A., Collins, K. H., Nicolucci, A. C., Urbanski, S. J., Hart, D. A., Vogel, H. J., Reimer, R. A. Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats. FASEB J. 33, 5153–5167 (2019). http://www.fasebj.org

Impaired Hypothalamic Microglial Activation in Offspring of Antibiotic-Treated Pregnant/Lactating Rats Is Attenuated by Prebiotic Oligofructose Co-Administration

“…In our study, maternal OFS intake was associated with significantly lower body weight in their offspring, despite offspring across all groups consuming similar caloric intake. This is comparable to previous work showing that maternal OFS consumption reduced body weight and fat mass in offspring at weaning [54] and attenuated hepatic steatosis in offspring fed a high fat/sucrose diet for 23 weeks [55]. Previous studies have demonstrated that prebiotics improve calcium absorption and increase bone mineral content and density [56][57][58].…”

“…In the steatosis study mentioned above [55], gut microbiota differences in prebiotic versus control offspring were most prominent at 3 weeks of age, diminished by 11 weeks of age and absent by 24 weeks of age [55]. Cox et al also found that after cessation of direct LDP, differences in microbial populations were transient, whereas the effects on various phenotypes such as body weight and obesity risk remained throughout life [25].…”

The Good, the Bad, and the Ugly of Pregnancy Nutrients and Developmental Programming of Adult Disease

“…It is well known that a balanced, diverse, and nutritious diet is universally recommended to meet nutritional needs to improve maternal and birth outcomes [137,138]; however, little is known whether supplementing with certain classes of nutrients in gestation can be beneficial on DOHaD-related disorders induced by various early-life insults in humans. In the current review, we only restrict to nutritional interventions during pregnancy and/or lactation periods as reprogramming strategies to prevent adult diseases of developmental origins in all sorts of animal models, some of which are listed in Table 2 [33,35,124,139,140,141,142,143,144,145,146,147,148,149,150]. Rats are the most commonly used species for developmental programming research.…”

“…Dietary fiber, one of the non-essential nutrients, has been used as reprogramming strategies to prevent developmental programming of hypertension [124], hepatic steatosis, and insulin resistance [150]. Maternal supplementation with inulin protected adult rat offspring born to dams fed with high-fructose diet against the developmental programming of hypertension [124].…”

Optimal Human Functioning Requires Exercise Across the Lifespan: Mobility in a 1g Environment Is Intrinsic to the Integrity of Multiple Biological Systems

“…Exercise can influence conditions such as type II diabetes onset and progression at the level of muscle-mediated insulinresistance (Way et al, 2016), as well as aspects of the metabolic syndrome and chronic inflammation associated with obesity, and many other aspects of the condition (Pedersen and Saltin, 2015). Nevertheless, even with obesity, epigenetic modifications can occur and progress over time (Desiderio et al, 2016;Pigeyre et al, 2016;Xu et al, 2016), and such changes may have transgenerational influences in both humans (Bays and Scinta, 2015) and preclinical models (Paul et al, 2019), so treating early obesity rather than long-term chronic obesity with exercise may yield substantially different outcomes for many individuals.…”