Offspring Gut Microbiota Research Articles

Sex-specific effects of PM2.5 maternal exposure on offspring's serum lipoproteins and gut microbiota

Fine particulate matter (PM2.5), which is known to impact public health, has received widespread attention recently. However, the long-term impact of maternal PM2.5 exposure remains unclear. To illuminate whether maternal PM2.5 exposure can affect serum lipoproteins and intestinal flora of offspring, mice received PM2.5 by intratracheal instillation during gestation and lactation. On postnatal day (PND) 35, serum lipoproteins of male and female pups were measured. Additionally, gut microbiota of offspring on PND 3, 10, 21 and 35 were measured by 16S rDNA sequencing of the colon contents. A higher serum triglyceride (TG) concentration in male offspring was observed in the exposed PM2.5 group (p < 0.05) compared with the control group, while there was no significant difference in lipoproteins for female offspring. On PND 35, Bacteroides, Desulfovibrio, and Anaerotruncus were enriched in the male offspring of the PM2.5-exposed group, and the control group had an increased abundance of Streptococcus. However, for female offspring on PND35, Clostridium XI was found to be enriched in the control group. A positive correlation between Bacteroides and serum TG concentration (r = 0.47, p = 0.02) was determined by Spearman's correlation analysis. These results suggest that serum TG and gut microbiota of offspring could be influenced by maternal PM2.5 exposure in a sex-specific manner. Abnormal lipid metabolism might be relevant to the changes of gut microbiota.

Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase

Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.

Intergenerational transfer of Dechlorane Plus and the associated long-term effects on the structure and function of gut microbiota in offspring

The gut microbiota has been shown to be highly involved in many vital physiological processes that play key roles in human health. The intergenerational transfer of Dechlorane Plus (DP) and the complex interaction between DP and microbiota has been poorly studied. Additionally, the structural and functional effects of DP on the gut microbiota have not been studied. This study aimed to investigate the DP transfer in Sprague-Dawley rats during pregnancy and the effects of DP exposure on gut microbiota, as detected by 16S rRNA gene sequencing. The results showed that excretion in feces is a very important elimination pathway of orally dosed DP. The main intergenerational transfer pathway of DP might be via lactation rather than transplacental transport. The 16S rRNA sequencing revealed that DP exposure could decrease the richness and diversity of gut microbiota, especially at the genus level. Furthermore, in DP exposure groups, the gut microbiota production of metabolites of short-chain fatty acids was dramatically increased. The results demonstrated that DP exposure not only altered the gut microbiota structures, but also immensely influenced metabolic functions, causing long-term impact to offspring. This data indicates that more attention should be paid to the long-term health effects related to DP exposure.

Maternal Glyphosate Exposure Causes Autism‐like Behaviors in Offspring through Increased Expression of Soluble Epoxide Hydrolase

The number of children with autism spectrum disorder (ASD) has increased dramatically since the 1980s. Epidemiological studies suggest that exposure to pesticides (i.e., glyphosate) during pregnancy might increase the risk for ASD in offspring. Recently, we demonstrated that soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids plays a key role in the development of ASD in offspring after maternal immune activation. In the present study, we found ASD‐like behavioral abnormalities in juvenile offspring after maternal glyphosate exposure. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure. Oxylipin analysis showed decreased levels of epoxy‐fatty acids (i.e., 8(9)‐EpETrE [8,9‐epoxy‐5Z,11Z,14Z‐eicosatrienoic acid] in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in juvenile offspring. The 16S rRNA analysis demonstrated abnormal composition of gut microbiota in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU to pregnant mothers from E5 to P21 could prevent social interaction deficits, increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal glyphosate exposure causes ASD‐like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH plays a key role in ASD‐like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH would represent a promising prophylactic target for ASD in offspring after maternal glyphosate exposure.Support or Funding InformationThis study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (to K.H., 17H04243), AMED (to K.H., JP19dm0107119), the National Institute of Environmental Health Sciences (NIEHS) R01 ES002710 (to B.D.H.), NIEHS Superfund Program P42 ES004699 (to B.D.H.).

The role of maternal diet on offspring gut microbiota development: A review.

In offspring, an adequate maternal diet is important for neurodevelopment. One mechanism by which maternal diet impacts neurodevelopment is through its dynamic role in the development of the gut microbiota. Communication between the gut, and its associated microbiota, and the brain is facilitated by the vagus nerve, in addition to other routes. Currently, the mechanisms through which maternal diet impacts offspring microbiota development are not well-defined. Therefore, this review aims to investigate the relationship between maternal diet during pregnancy and offspring microbiota development and its impact on neurodevelopment. Both human and animal model studies were reviewed to understand the impact of maternal diet on offspring microbiota development and potential consequences on neurodevelopment. In the period after birth, as reported in both human and model system studies, maternal diet impacts offspring bacterial colonization (e.g., decreased presence of Lactobacillus reuteri as a result of a high-fat maternal diet). It remains unknown whether these changes persist into adulthood and whether they impact vulnerability to disease. Therefore, further long-term studies are required in both human and model systems to study these changes. Our survey of the literature indicates that maternal diet influences early postnatal microbiota development, which in turn, may serve as a mechanism through which maternal diet impacts neurodevelopment.

Goat Milk Consumption Enhances Innate and Adaptive Immunities and Alleviates Allergen-Induced Airway Inflammation in Offspring Mice.

Goat milk (GM), as compared to cow milk (CM), is easier for humans to digest. It also has antioxidant and anti-inflammatory effects and can improve minor digestive disorders and prevent allergic diseases in infants. It is unclear whether GM consumed in pregnant mothers has any protective effects on allergic diseases in infants. In this experimental study with mice, we found GM feeding enhanced immunoglobulin production, antigen-specific (ovalbumin, OVA) immune responses, and phagocytosis activity. The GM-fed mice had an increasing proportion of CD3+ T lymphocytes in the spleen. Splenocytes isolated from these animals also showed significantly increased production of cytokines IFN-γ and IL-10. More importantly, GM feeding during pregnancy and lactation periods can confer protective activity onto offspring by alleviating the airway inflammation of allergic asthma induced by mite allergens. There was a remarkably different composition of gut microbiota between offspring of pregnant mice fed with water or with milk (GM or CM). There was a greater proportion of beneficial bacterial species, such as Akkermansia muciniphila, Bacteroides eggerthii, and Parabacteroides goldsteinii in the gut microbiota of offspring from GM- or CM-fed pregnant mice compared to the offspring of water-fed pregnant mice. These results suggested that improving the nutrition of pregnant mice can promote immunological maturation and colonization of gut microbiota in offspring. This mother-to-child biological action may provide a protective effect on atopy development and alleviate allergen-induced airway inflammation in offspring.

Microbial Reconstitution Reverses Early Female Puberty Induced by Maternal High-fat Diet During Lactation.

Recent work shows that gut microbial dysbiosis contributes to the risk of obesity in children whose mothers consume a high-fat diet (HFD) during both gestation and lactation or during gestation alone. Obesity predisposes children to developing precocious puberty. However, to date, no study has examined how maternal HFD (MHFD) during lactation regulates the gut microbiota (GM), pubertal timing, and fertility of offspring. Here, we found that MHFD during lactation markedly altered the GM of offspring. The pups developed juvenile obesity, early puberty, irregular estrous cycles, and signs of disrupted glucose metabolism. Remarkably, permitting coprophagia between MHFD and maternal normal chow offspring successfully reversed the GM changes as well as early puberty and insulin insensitivity. Our data suggest that microbial reconstitution may prevent or treat early puberty associated with insulin resistance.

Oral administration of Lactobacillus fermentum post-weaning improves the lipid profile and autonomic dysfunction in rat offspring exposed to maternal dyslipidemia.

Maternal dyslipidemia alters the gut microbiota composition and contributes to the development of arterial hypertension (AH) in offspring. Here, we evaluated the effects of a new Lactobacillus fermentum probiotic formulation given post-weaning on cardiometabolic parameters and gut microbiota in male and female rat offspring from dams exposed to maternal dyslipidemia during pregnancy and lactation. Wistar rats (n = 14) were fed with a control diet (CTL = 7) or a dyslipidemic diet (DLP = 7) during pregnancy and lactation. After weaning, male and female offspring received a standard diet up to 90 days of life. Rats were allocated into three groups: CTL group + saline solution (n = 14); DLP group + saline solution (n = 14) and DLP group receiving a probiotic cocktail (n = 14). A vehicle or probiotic formulation containing L. fermentum 139, L. fermentum 263 and L. fermentum 296 (ratio 1 : 1 : 1, 1 × 109 CFU mL-1) was administered daily by oral gavage for 8 weeks. The intervention with the probiotic formulation of L. fermentum in male and female offspring reduced total cholesterol (TC) and increased HDL-c, but did not affect the insulin resistance induced by maternal dyslipidemia. Additionally, the male and female rats that received the probiotic formulation of L. fermentum demonstrated improvement in fecal Lactobacillus sp. counts, blood pressure and sympathetic tone, without affecting baroreflex modulation. The probiotic formulation containing L. fermentum improved the lipid profile and autonomic dysfunction in male and female offspring exposed to maternal dyslipidemia.

Maternal Dietary Fiber Composition during Gestation Induces Changes in Offspring Antioxidative Capacity, Inflammatory Response, and Gut Microbiota in a Sow Model.

To study the effects of maternal dietary fiber composition during gestation on offspring antioxidant capacity, inflammation, and gut microbiota composition, we randomly assigned 64 gilts to four treatments and administered diets with an insoluble/soluble fiber ratio of 3.89 (R1), 5.59 (R2), 9.12 (R3), and 12.81 (R4). Sow samples (blood and feces at gestation 110) and neonatal samples (blood, liver, and colonic contents) were collected. The results showed that sows and piglets in R1 and R2 had higher antioxidant enzyme activity and lower pro-inflammatory factor levels than those in R3 and R4. Moreover, piglets in R1 and R2 had higher liver mRNA expression of Nrf2 and HO-1 and lower NF-κB than piglets in R4. Interestingly, maternal fiber composition not only affected the production of short-chain fatty acids (SCFAs) in sow feces but also influenced the concentrations of SCFAs in the neonatal colon. Results of high-throughput sequencing showed that piglets as well as sows in R1 and R2 had microbial community structures distinct from those in R3 and R4. Therefore, the composition of dietary fiber in pregnancy diet had an important role in improving antioxidant capacity and decreasing inflammatory response of mothers and their offspring through modulating the composition of gut microbiota.

The microbiota composition of the offspring of patients with gestational diabetes mellitus (GDM).

The microbiota composition of the offspring of women with gestational diabetes mellitus (GDM), a common pregnancy complication, is still little known. We investigated whether the GDM offspring gut microbiota composition is associated with the maternal nutritional habits, metabolic variables or pregnancy outcomes. Furthermore, we compared the GDM offspring microbiota to the microbiota of normoglycemic-mother offspring. Fecal samples of 29 GDM infants were collected during the first week of life and assessed by 16S amplicon-based sequencing. The offspring’s microbiota showed significantly lower α-diversity than the corresponding mothers. Earlier maternal nutritional habits were more strongly associated with the offspring microbiota (maternal oligosaccharide positively with infant Ruminococcus, maternal saturated fat intake inversely with infant Rikenellaceae and Ruminococcus) than last-trimester maternal habits. Principal coordinate analysis showed a separation of the infant microbiota according to the type of feeding (breastfeeding vs formula-feeding), displaying in breast-fed infants a higher abundance of Bifidobacterium. A few Bacteroides and Blautia oligotypes were shared by the GDM mothers and their offspring, suggesting a maternal microbial imprinting. Finally, GDM infants showed higher relative abundance of pro-inflammatory taxa than infants from healthy women. In conclusion, many maternal conditions impact on the microbiota composition of GDM offspring whose microbiota showed increased abundance of pro-inflammatory taxa.

Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota

Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.

Heat stress affects fecal microbial and metabolic alterations of primiparous sows during late gestation

BackgroundHeat stress (HS) jeopardizes intestinal barrier functions and augments intestinal permeability in pigs. However, whether HS-induced maternal microbial and metabolic changes in primiparous sows during late gestation remains elusive. We present here, a study investigating the fecal microbial and metabolic responses in late gestational primiparous sows when exposed to HS.MethodsTwelve first-parity Landrace × Large White F1 sows were randomly assigned into two environmental treatments including the thermoneutral (TN) (18–22 °C; n = 6) and HS (28–32 °C; n = 6) conditions. Both treatments were applied from 85 d of gestation to farrowing. The serum and feces samples were collected on d 107 of gestation, for analyses including intestinal integrity biomarkers, high-throughput sequencing metagenomics, short-chain fatty acid (SCFA) profiles and nontargeted metabolomics.ResultsOur results show that HS group has higher serum Heat shock protein 70 (HSP70), lipopolysaccharide (LPS) and lipopolysaccharide-binding protein (LBP) levels. The gut microbial community can be altered upon HS by using β-diversity and taxon-based analysis. In particular, the relative abundance of genera and operational taxonomic units (OTUs) related to Clostridiales and Halomonas are higher in HS group, the relative abundance of genera and OTUs related to Bacteroidales and Streptococcus, however, are lower in HS group. Results of metabolic analysis reveal that HS lowers the concentrations of propionate, butyrate, total SCFA, succinate, fumarate, malate, lactate, aspartate, ethanolamine, β-alanine and niacin, whereas that of fructose and azelaic acid are higher in HS group. These metabolites mainly affect propanoate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism, β-alanine metabolism, pantothenate and CoA biosynthesis, tricarboxylic acid cycle (TCA) and nicotinate and nicotinamide metabolism. Additionally, correlation analysis between significant microbes and metabolites indicated that the HS-induced microbiota shift is likely the cause of changes of intestinal metabolism.ConclusionsTaken together, we reveal characteristic structural and metabolic changes in maternal gut microbiota as a result of late gestational HS, which could potentially provide the basis for further study on offspring gut microbiota and immune programming.

Maternal supplementation with a synbiotic has distinct outcomes on offspring gut microbiota formation in A/J and C57BL/6 mice, differentially affecting airway inflammatory cell infiltration and mucus production

• Maternal synbiotics modulate gut microbiota depending on host genetics. • Maternal synbiotics affect allergic outcomes in A/J and B6 offspring differently. • Microbiota diversity was not enough to regulate airway eosinophilia in allergic A/J mice. Emerging evidence has shown that the maternal diet influences the microbiota. Our objective was to elucidate whether synbiotic consumption during the perinatal period equally modulates offspring gut microbiota in the A/J and C57BL/6 and affects airway inflammatory cell infiltration. We administered the synbiotic to the dam throughout the whole perinatal period. To analyze the influence of gut microbiota changes on offspring health, we induced allergic airway inflammation on offspring. Twenty-four hours after the last ovalbumin challenge, pulmonary inflammation was analyzed. Perinatal synbiotic supplementation reduced eosinophilic inflammation and mucus production only in the C57BL/6 offspring. Synbiotic supplementation during the perinatal period increased the Lactobacillus genera, which could be associated with the immune regulatory effects observed in the C57BL/6 offspring. Interestingly, synbiotic supplementation increased the diversity of gut microbiota in the A/J offspring without improving airway inflammation, indicating that diversity itself was not sufficient to regulate experimental lung inflammation.

Early genistein exposure of California mice and effects on the gut microbiota-brain axis.

Human offspring encounter high amounts of phytoestrogens, such as genistein (GEN), through maternal diet and soy-based formulas. Such chemicals can exert estrogenic activity and thereby disrupt neurobehavioral programming. Besides inducing direct host effects, GEN might cause gut dysbiosis and alter gut metabolites. To determine whether exposure to GEN affects these parameters, California mice (Peromyscus californicus) dams were placed 2 weeks prior to breeding and throughout gestation and lactation on a diet supplemented with GEN (250 mg/kg feed weight) or AIN93G phytoestrogen-free control diet (AIN). At weaning, offspring socio-communicative behaviors, gut microbiota and metabolite profiles were assayed. Exposure of offspring to GEN-induced sex-dependent changes in gut microbiota and metabolites. GEN exposed females were less likely to investigate a novel female mouse when tested in a three-chamber social test. When isolated, GEN males and females exhibited increased latency to elicit their first call, suggestive of reduced motivation to communicate with other individuals. Correlation analyses revealed interactions between GEN-induced microbiome, metabolome and socio-communicative behaviors. Comparison of GEN males with AIN males revealed the fraction of calls above 20 kHz was associated with daidzein, α-tocopherol, Flexispira spp. and Odoribacter spp. Results suggest early GEN exposure disrupts normal socio-communicative behaviors in California mice, which are otherwise evident in these social rodents. Such effects may be due to GEN disruptions on neural programming but might also be attributed to GEN-induced microbiota shifts and resultant changes in gut metabolites. Findings indicate cause for concern that perinatal exposure to GEN may detrimentally affect the offspring microbiome-gut-brain axis.

Abnormality in Maternal Dietary Calcium Intake During Pregnancy and Lactation Promotes Body Weight Gain by Affecting the Gut Microbiota in Mouse Offspring.

To investigate the effects of calcium status in early life on adult body weight and the underlying mechanisms involved in gut microbiota and related lipid metabolism. Three to four-week-old C57BL/6J female mice were fed diets with normal, insufficient, and excessive calcium respectively throughout pregnancy and lactation. The weaning male pups were fed with a high-fat diet for 16 weeks, with a normal-fat diet to the normal calcium group as control.The offspring fecal microbiota was analyzed by 16S rRNA high-throughput sequencing, and mRNA expressions of genes were determined by the real-time RT-PCR. Maternal insufficient or excessive calcium intake exacerbated offspring obesity, with expressional changes in the Fasn, Acc1, LPL, Fiaf, and PPAR-α genes in the liver or fat. The dysbiosis in gut microbiota in obese offspring was exacerbated by maternal imbalanced calcium intake, with increased Firmicutes and decreased Bacteroidetes in calcium insufficiency, and decreased Verrucomicrobia in calcium excess. Several genera, including Bacteroides, were reduced, and Lachnospiraceae and Lactobacillus were increased by maternal insufficient or excessive calcium intake. Imbalance in maternal calcium intake promotes body weight gain in offspring, which may be mediated by calcium's modulation on the gut microbiota and lipid metabolism.

New Insights into Porcine Milk N-Glycome and the Potential Relation with Offspring Gut Microbiome.

N-Glycans are an important source of milk oligosaccharides. In addition to free oligosaccharides found in milk, N-glycans can also be utilized by gut microbes. A potential for milk N-glycans to act as gut microbe regulators in suckling animals has attracted considerable attention; however, sow milk N-glycans and their potential effects upon the piglet's gut microbes in vivo remain unknown. In the present study, we profiled the milk N-glycans of Meishan and Yorkshire sows during lactation using UPLC and a mass spectrometry-based glycome method, and we explored the correlations between milk N-glycans and offspring gut microbiota. Twenty-two N-glycan structures were identified in sow milk, among which 36% (8 out of 22) were fucosylated, 41% (9 out of 22) were sialylated, and 14% (3 out of 22) were high mannosylated. An N-glycan with a NeuGc structure (namely PNO20, GlcNAc4-Man3-Gal2-Fuc-Neu5Gc) was identified in sow milk for the first time. No compositional differences between the two breeds or between different lactation times were found in porcine milk N-linked oligosaccharides (PNOs); however, the abundances of different structures within this class did vary. The relative abundances of fucosylated PNO3 (GlcNAc4-Man3-Fuc) and sialylated PNO18 (GlcNAc4-Man3-Gal2-NeuAc) increased during lactation, and Meishan sows demonstrated a higher ( P < 0.05) abundance of mannosylated PNO10 (GlcNAc2-Man6) and sialylated PNO17 (GlcNAc5-Man3-Gal-NeuAc) than Yorkshire sows. Apparent correlations between milk N-glycans and offspring gut microbial populations were found; for example, mannosylated PNO21 (GlcNAc2-Man9) was positively correlated with OTU706 ( Lactobacillus amylovorus) and OTU1380 ( Bacteroides uniformis). Overall, our results indicate that the milk N-glycome of Meishan and Yorkshire sows differs in N-glycome characteristics and that this is correlated to abundances of certain piglet gut microbes. These findings provide a reference for future elucidation of the involvement of gut microbes in milk N-glycan metabolism, which is important to the health both of large domestic animals and humans.

Impacts of Diet and Exercise on Maternal Gut Microbiota Are Transferred to Offspring.

Background: It is well established that maternal exercise during pregnancy improves metabolic outcomes associated with obesity in mothers and offspring, however, its effects on the gut microbiota of both mother and offspring, are unknown. Here, we investigated whether wheel running exercise prior to and during pregnancy and prolonged feeding of an obesogenic diet were associated with changes in the gut microbiomes of Sprague-Dawley rat dams and their offspring. Female rats were fed either chow or obesogenic diet, and half of each diet group were given access to a running wheel 10 days before mating until delivery, while others remained sedentary. 16S rRNA gene amplicon sequencing was used to assess gut microbial communities in dams and their male and female offspring around the time of weaning.Results: Statistical analyses at the operational taxonomic unit (OTU) level revealed that maternal obesogenic diet decreased gut microbial alpha diversity and altered abundances of bacterial taxa previously associated with obesity such as Bacteroides and Blautia in dams, and their offspring of both sexes. Distance based linear modeling revealed that the relative abundances of Bacteroides OTUs were associated with adiposity measures in both dams and offspring. We identified no marked effects of maternal exercise on the gut microbiota of obesogenic diet dams or their offspring. In contrast, maternal exercise decreased gut microbial alpha diversity and altered the abundance of 88 microbial taxa in offspring of control dams. Thirty of these taxa were altered in a similar direction in offspring of sedentary obesogenic vs. control diet dams. In particular, the relative abundances of Oscillibacter OTUs were decreased in offspring of both exercised control dams and sedentary obesogenic diet dams, and associated with blood glucose concentrations and adiposity measures. Analyses of predicted bacterial metabolic pathways inferred decreased indole alkaloid biosynthesis in offspring of both obesogenic diet and exercised control dams.Conclusions: Our data suggest that maternal exercise prior to and during pregnancy resulted in gut dysbiosis in offspring of control dams. Importantly, alterations in the maternal gut microbiota by obesogenic diet or obesity were transferred to their offspring.

Maternal High Fat Diet Alters Gut Microbiota of Offspring and Exacerbates DSS-Induced Colitis in Adulthood

Background: Accumulating evidence shows that high fat diet is closely associated with inflammatory bowel disease. However, the effects and underlying mechanisms of maternal high fat diet (MHFD) on the susceptibility of offspring to colitis in adulthood lacks confirmation.Methods: C57BL/6 pregnant mice were given either a high fat (60 E% fat, MHFD group) or control diet [10 E% fat, maternal control diet (MCD) group] during gestation and lactation. The intestinal development, mucosal barrier function, microbiota, and mucosal inflammation of 3-week old offspring were assessed. After weaning all mice were fed a control diet until 8 weeks of age when the microbiota was analyzed. Offspring were also treated with 2% DSS solution for 5 days and the severity of colitis was assessed.Results: The offspring in MHFD group were significantly heavier than those in MCD group only at 2–4 weeks of age, while no differences were found in the body weight between two groups at other measured time points. Compared with MCD group, MHFD significantly inhibited intestinal development and disrupted barrier function in 3-week old offspring. Although H&E staining showed no obvious microscopic inflammation in both groups of 3-week old offspring, increased production of inflammatory cytokines indicated low-grade inflammation was induced in MHFD group. Moreover, fecal analysis of the 3-week old offspring indicated that the microbiota compositions and diversity were significantly changed in MHFD group. Interestingly after 5 weeks consumption of control diet in both groups, the microbiota composition of offspring in MHFD group was still different from that in MCD group, although the bacterial diversity was partly recovered at 8 weeks of age. Finally, after DSS treatment in 8-week old offspring, MHFD significantly exacerbated the severity of colitis and increased the production of proinflammatory cytokine.Conclusions: Our data reveal that MHFD in early life can inhibit intestinal development, induce dysbiosis and low-grade inflammation and lead to the disruption of intestinal mucosal barrier in offspring, and enhance DSS-induced colitis in adulthood.

Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota

BackgroundThe early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes.ResultsHere, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding.ConclusionsOur data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome.

Diet induced maternal obesity affects offspring gut microbiota and persists into young adulthood.

Accumulating evidence suggests that diet could shape the host gut microbiome composition. Herein, we investigated the effects of maternal high fat diet (HFD) consumption on the gut microbiota and serum profile of mice offspring, and attempted to explore the beneficial roles of maternal probiotics intervention. Female C57BL/6J mice were fed with normal diet, HFD or HFD with daily probiotics (B. breve DM8310, L. acidophilus DM8302, L. casei DM8121 and S. thermophilus DM8309) by gavage starting 6 weeks prior to breeding and continued throughout gestation and lactation. Pups of HFD dams had higher levels of total cholesterol (TC), low-density lipoprotein (LDL), glucose, insulin and leptin compared to those of chow-fed dams. Maternal probiotics intervention resulted in a decrease in the lipid levels in all the pups, while the glucose, insulin and leptin levels were decreased only in adult female pups compared to those from HFD-fed dams; the decreased levels were similar to those in the pups of chow-fed dams. In line with these plasma changes, maternal HFD persistently altered the composition of the offspring gut microbiota in a sex specific way. Maternal probiotics intervention could ameliorate gut microbiota dysbiosis in the offspring. Such intervention showed better effects particularly for the female pups at adulthood. In conclusion, maternal HFD-induced gut microbiota dysbiosis and metabolic disorder could persist through the adulthood of the offspring. Maternal probiotics intervention can negate the detrimental effects of maternal HFD on the gut microbiota and metabolism in the offspring in a sex specific way.