Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre‐conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short‐chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.

Dietary fiber promotes a healthy gut microbiome and shows promise in attenuating the unfavorable microbial changes resulting from a high‐fat/sucrose (HFS) diet. High‐fiber diets consisting of oligofructose alone (HFS/O) or in combination with β‐glucan (HFS/OB), resistant starch (HFS/OR), or β‐glucan and resistant starch (HFS/OBR) were fed to diet‐induced obese rats for 8 weeks to determine if these fibers could attenuate the obese phenotype. Only the HFS/O group displayed a decrease in body weight and body fat, but all fiber interventions improved insulin sensitivity and cognitive function. The HFS/O diet was the least effective at improving cognitive function and only the HFS/OB group showed improvements in glucose tolerance, thus highlighting the differential effects of fiber types. Hippocampal cytokines (IL‐6, IL‐10) were more pronounced in the HFS/OB group which coincided with the most time spend in the open arms of the elevated plus maze. All fiber groups showed an increase in beneficial Bifidobacterium and Lactobacillus abundance while the HFS group showed higher abundance of Clostridium. Fecal microbiota transplant from fiber‐treated rats into germ‐free mice did not alter body composition in the mice but did result in a higher abundance of Bacteroides in the HFS/O and HFS/OB groups compared to HFS. The HFS/OB recipient mice also had higher insulin sensitivity compared to the other groups. This study highlights the influence of dietary fiber type on metabolic and cognitive outcomes suggesting that the type of supplementation (single or combined fibers) could be tailored to specific targeted outcomes.

ScopeAntibiotics in early life disrupt microbiota and increase obesity risk. Dietary agents such as prebiotics may reduce obesity risk. The authors examine how antibiotics administered with/without prebiotic oligofructose, alter metabolic and microbial outcomes in pregnant rats and their offspring.Methods and ResultsPregnant rats are randomized to: 1) Control, 2) Antibiotic (ABT), 3) Prebiotic (PRE), 4) Antibiotic+Prebiotic (ABT+PRE) during the 3rd week of pregnancy and lactation. Offspring were fed a high fat/high sucrose (HFS) diet from 9–17 weeks of age to unmask obesity risk. ABT dams had higher body weight, body fat and leptin during lactation than all other groups. Prebiotics attenuate these outcomes and increase cecal Bifidobacterium. ABT offspring have higher body weight, fat mass, and liver triglycerides after HFS diet, with a stronger phenotype in males; prebiotics attenuate these. At weaning, male ABT offspring have lower Lactobacillus while PRE and ABT+PRE offspring had higher Bifidobacterium and Collinsella. Fecal microbiota transfer of adult offspring cecal matter could not reliably transfer the obese ABT phenotype.ConclusionsAntibiotic use during pregnancy/lactation increases adiposity and impairs post‐partum weight loss in dams. Co‐administering prebiotics with antibiotics in rat dams prevented obesity risk in offspring and is associated with altered gut microbiota.

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