Fig. 1: Paternal gut dysbiosis probabilistically triggers major F1 phenotypes.
From: Paternal microbiome perturbations impact offspring fitness
a, Schematic showing the strategy for induced paternal dysbiosis and recovery using nABX. b, Quantification of microbial taxa richness in males after 6 weeks of nABX treatment and during the recovery (rec) time course, by 16S rRNA sequencing (CON t0 = 18, 6 wk = 18, 6 wk + 4 rec = 14, 6 wk + 8 rec = 11; nABX t0 = 19, 6 wk = 12, 6 wk + 4 rec = 13, 6 wk + 8 rec = 12 individuals per timepoint). Bar represents median, whiskers 1.5× interquartile range. c, Body weight of F1 offspring at postnatal days P3 and P15 according to paternal nABX treatment. P value by two-tailed nested (hierarchical) t-test (CON n = 172, nested into N = 26 fathers; nABX n = 181 nested into N = 28 fathers). Bar indicates mean. d, Representative images of SGR phenotype in F1 offspring from dysbiotic fathers (nABX-treated). e, Forest plot showing the log OR of risk for abnormal body-weight classes in offspring that survive to P15. Null effect is represented by a vertical line for which OR value is 1. Whiskers indicate 95% CI, P value by two-sided Chi-square test (mortality P = 0.0001; SGR P = 0.044). f, Kaplan–Meier plot showing postnatal survival of F1 progeny depending on paternal nABX treatment regime (CON n = 179; nABX n = 199). P value by Mantel–Cox (log-rank) test. g, PCA of transcriptomes from F1 brains derived from control or nABX sires. The nABX offspring are stratified by normal or SGR phenotype. SGR not observed in control offspring. h, Heatmap showing expression of top upregulated and downregulated genes in F1 SGR brains, from independent litters sired by nABX-treated fathers. i, Left, OR of F1 susceptibility for abnormal body weight and mortality when sired by males with dysbiosis induced by 6 weeks of treatment with general antibiotics (avaABX). Whiskers indicate 95% CI, P value by two-sided Chi-square test (mortality P = 0.014; SGR P = 0.038). Right, Kaplan–Meier plot showing postnatal survival of F1 progeny from avaABX-treated males. j, Left, OR of F1 risk for abnormal body weight when sired by males with dysbiosis induced by 6 weeks of bowel cleansing with PEG laxative. Whiskers indicate 95% CI, P value by two-sided Chi-square test (mortality P = 0.013; SGR P = 0.014). Right, Kaplan–Meier plot showing survival of F1 progeny from PEG-treated males. n, offspring; N, litters; ND, not detected.
