Maternal obesity significantly increases the risk of adverse outcomes for the mother and fetus. Fermented wheat germ (FWG) has demonstrated the potential to improve metabolic disorders, yet its effects have not been explored in maternal obesity models. This study investigated the ameliorating impact of FWG in rats with maternal obesity, focusing on its mechanisms through biochemical, gut microbiome, and serum metabolomics analysis. The results demonstrated that FWG was more effective than wheat germ in reducing body weight gain and fat accumulation, improving glycolipid metabolism disorders, and alleviating inflammation. Specifically, FWG modulated the composition of gut microbiota by fostering the growth of beneficial bacteria (e.g., Corynebacterium) while suppressing genera associated with maternal obesity (e.g., Blautia, Akkermansia, Dorea_A, and Faecousia). Furthermore, FWG modified high-fat diet-induced metabolites, primarily affecting pyrimidine metabolism and amino acid metabolism. These findings suggest that FWG may serve as a promising dietary intervention for mitigating maternal obesity and improving pregnancy outcomes.

Microorganisms play an important role in regulating various biological processes in our bodies. In women, abnormal changes in the reproductive tract microbiome are associated with various gynecological diseases and infertility. Recent studies suggest that patients with recurrent implantation failure (RIF) have a reduced genus Lactobacillus population, a predominant bacterial species in the vagina and uterus that protects the reproductive tract from pathogenic bacterial growth via the production of various metabolites (e.g., lactic acid, bacteriocin, and H2O2). Moreover, a higher percentage of pathogenic bacteria genera, including Atopobium, Gardnerella, Prevotella, Pseudomonas, and Streptococcus, was found in the uterus of RIF patients. This review aimed to examine the role of pathogenic bacteria in RIF, determine the factors altering the endometrial microbiome, and assess the impact of the microbiome on embryo implantation in RIF. Several factors can influence microbial balance, including the impact of extrinsic elements such as semen and antibiotics, which can lead to dysbiosis in the female reproductive tract and affect implantation. Additionally, probiotics such as Lacticaseibacillus rhamnosus were reported to have clinical potential in RIF patients. Future studies are needed to develop targeted probiotic therapies to restore microbial balance and enhance fertility outcomes. Research should also focus on understanding the mechanisms by which microorganisms generate metabolites to suppress pathogenic bacteria for embryo implantation. Identifying these interactions may contribute to innovative microbiome-based interventions for reproductive health.

The maternal microbiome is emerging as an important factor that influences the neurological health of mothers and their children. Recent studies highlight how microbial communities in the maternal gut can shape early-life development in ways that inform long-term health trajectories. Research on the neurodevelopmental effects of maternal microbiomes is expanding our understanding of the microbiome-gut-brain axis to include signaling across the maternal-offspring unit during the perinatal period. In this Review, we synthesize existing literature on how the maternal microbiome modulates brain function and behavior in both mothers and their developing offspring. We present evidence from human and animal studies showing that the maternal microbiome interacts with environmental factors to impact risk for neurodevelopmental abnormalities. We further discuss molecular and cellular mechanisms that facilitate maternal-offspring crosstalk for neuromodulation. Finally, we consider how advancing understanding of these complex interactions could lead to microbiome-based interventions for promoting maternal and offspring health.

Despite the association between the gut dysbiosis and metabolic disorders, the main bacterial phylum in the first trimester of pregnancy that predisposes mothers to gestational diabetes mellitus (GDM) in the second trimester is not clear around the world.

Three-hundred healthy women aged 18-40 years who were in the first trimester were participated in this cohort study and followed to the screening time for GDM diagnosis (in 24-28 weeks of pregnancy). Stool samples were gathered in the first trimester. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Groups. In total, thirty mothers were diagnosed with GDM. Controls (N = 60) were selected from non-GDM participants matching to the GDM in terms of pre-pregnancy weight, weight gain, dietary intake and familial history of diabetes. The dominant phylum population was determined based on 16SrRNA gene expression.

Mothers with lower Bacteroidetes and Actinobacteria population in the first trimester were more susceptible to GDM in the screening time (p < 0.001 and p < 0.001). The Firmicutes to Bacteroidetes ratio was significantly higher in mothers with GDM than the controls (p < 0.001). A significant negative correlation was observed between the gut Bacteroidetes (p < 0.001, p < 0.001, p < 0.001) and Actinobacteria (p = 0.004, p < 0.001, p = 0.02) population in the first trimester with the the serum FBS, 1 h-PG and 2 h-PG levels in the screening time. However, the gut Firmicutes to Bacteroidetes ratio (p = 0.003, p = 0.01) showed a significant positive correlation with serum FBS and 1 h-PG levels.

A higher Bacteroidetes and Actinobacteria population in the gut of mothers at the first trimester was associated with lower risk of GDM in the screening time. Higher Firmicutes to Bacteroidetes ratio in the gut of mothers was associated with fasting and 1-h glucose intolerance in the screening time.

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of postpartum metabolic disease. Based on the important role that the intestinal microbiota plays in blood glucose regulation and insulin sensitivity, supplementation of probiotic and postbiotic strains could improve glucose metabolism and tolerance in GDM.

56 4-week-old female C57BL/6J-mice were divided into 4 groups (n = 14 animals/group): control (CNT), high-fat/high-sucrose (HFS), pA1c® alive (pA1c®) and heat-inactivated pA1c® (pA1c®HI). Serum biochemical parameters were analyzed, gene expression analyses were conducted, and fecal microbiota composition was evaluated by shot-gun sequencing.

pA1c®- and pA1c® HI-supplemented groups presented reduced fasting blood glucose levels and reduced insulin resistance during gestation and exhibited lower visceral adiposity and increased muscle tissue, together with an improvement in intrahepatic TGs content and ALT levels. Liver gene expression analyses demonstrated that pA1c® and pA1c® HI activities were mediated by modulation of the insulin receptor, but also by an overexpression of beta-oxidation genes, and downregulation of fatty acid biosynthesis genes. Shot-gun metagenomics demonstrated that Pediococcus acidilactici was detected in the feces of all the pA1c® and pA1c® HI-group after the supplementation period (75 % of the microbial profile was Pediococcus acidilactici) in only nine weeks of supplementation, and modulated gut microbiota composition.

These results may be considered as future perspectives for the development of preventive, even therapeutic options for GDM based on hyperglycemia reduction, blood glucose regulation, hepatic steatosis attenuation and insulin resistance alleviation.

The development of the fetal immune response is a highly complex process. In the present review, we describe the development of the fetal immune response and the role of the maternal gut bacteria in this process. In contrast to the previous belief that the fetal immune response is inert, it is now thought that the fetal immune response is uniquely tolerant to maternal and allo-antigens, but able to respond to infectious agents, such as bacteria. This is accomplished by the development of T cells toward regulatory T cells rather than toward effector T cells, but also by the presence of functional innate immune cells, such as monocytes and NK cells. Moreover, in fetuses there is different programming of CD8 + T cells and memory T cells toward innate immune cells rather than to adaptive immune cells. The maternal gut bacteria are important in shaping the fetal immune response by producing bacterial products and metabolites that pass the placenta into the fetus and influence development of the fetal immune response. Insight into how and when these products affect the fetal immune response may open new treatment options with pre- or probiotics to affect the maternal gut bacteria and therewith the fetal immune response.

The prevalence of gestational diabetes mellitus (GDM), a condition that is widespread globally, is increasing. The relationship between the gut microbiota and GDM has been a subject of research for nearly two decades, yet there has been no bibliometric analysis of this correlation. This study aimed to use bibliometrics to explore the relationship between the gut microbiota and GDM, highlighting emerging trends and current research hotspots in this field.

A total of 394 papers were included in the analysis. China emerged as the preeminent nation in terms of the number of publications on the subject, with 128 papers (32.49%), whereas the United States had the most significant impact, with 4,874 citations. The University of Queensland emerged as the most prolific institution, contributing 18 publications. Marloes Dekker Nitert was the most active author with 16 publications, and Omry Koren garnered the most citations, totaling 154. The journal Nutrients published the most studies (28 publications, 7.11%), whereas PLoS One was the most commonly co-cited journal, with a total of 805 citations. With respect to keywords, research focuses can be divided into 4 clusters, namely, "the interrelationship between the gut microbiota and pregnancy, childbirth," "the relationship between adverse metabolic outcomes and GDM," "the gut microbiota composition and metabolic mechanisms" and "microbiota and ecological imbalance." Key areas of focus include the interactions between the gut microbiota and individuals with GDM, as well as the formation and inheritance of the gut microbiota. Increasing attention has been given to the impact of probiotic supplementation on metabolism and pregnancy outcomes in GDM patients. Moreover, ongoing research is exploring the potential of the gut microbiota as a biomarker for GDM. These topics represent both current and future directions in this field.

This study provides a comprehensive knowledge map of the gut microbiota and GDM, highlights key research areas, and outlines potential future directions.

This study aims to explore the mechanism of Yangxuerongjin pill (YXRJP) in the treatment of diabetic peripheral neuropathy (DPN) by network pharmacology and metabolomics technology combined with animal experiments, and to provide scientific basis for the treatment of DPN.

In this study, network pharmacology analysis was applied to identify the active compounds, core targets and signal pathways, which might be responsible for the effect of DPN. The DPN model was established by high-fat diet combined with streptozotocin (STZ) injection, and the rats were given administration for 12 weeks. The body weight, thermal withdrawal latency (TWL), sciatic motor nerve conduction velocity (MNCV), biochemical indexes, pathological sections of sciatic nerve, oxidative stress factors and the expression levels of neuroprotection-related proteins were detected. Metabolomics technology was used to analyze the potential biomarkers and potential metabolic pathways in DPN treated with YXRJP.

The results of network pharmacology showed that YXRJP could treat DPN through baicalin, β-sitosterol, 7-methoxy-2-methylisoflavone, aloe-emodin and luteolin on insulin resistance, Toll-like receptor (TLR), tumor necrosis factor (TNF) and other signaling pathways. YXRJP can prolong the TWL, increase the MNCV of the sciatic nerve, alleviate the injury of the sciatic nerve, reduce the levels of triglyceride (TG), improve the expression of Insulin-like growth factor 1 (IGF-1) protein in the sciatic nerve, and reduce the expression of protein kinase B (AKT) protein. Metabolomics results showed that the potential metabolic pathways of YXRJP in the treatment of DPN mainly involved amino acid metabolism such as arginine, alanine, aspartic acid, lipid metabolism and nucleotide metabolism.

YXRJP can effectively improve the symptoms of DPN rats and reduce nerve damage. The effects are mainly related to reducing oxidative stress injury, promoting the expression of neuroprotection-related proteins, reducing the expression of inflammation-related proteins, and affecting amino acid metabolism, lipid metabolism, and nucleotide metabolism pathways. Our findings revealed that YXRJP has a good therapeutic potential for DPN, which provides a reference for further studies on YXRJP.

Metabolic diseases, including obesity, dyslipidemia, and type 2 diabetes, have become severe challenges worldwide. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that an adverse intrauterine environment can increase the risk of metabolic disorders in offspring. Studies have demonstrated that maternal exercise is an effective intervention for improving the offspring metabolic health. However, the pathways through which exercise works are unclear. It has been reported that the gut microbiota mediates the effect of maternal exercise on offspring metabolism, and epigenetic modifications have also been proposed to be important molecular mechanisms. Microbial metabolites can influence epigenetics by providing substrates for DNA or histone modifications, binding to G-protein-coupled receptors to affect downstream pathways, or regulating the activity of epigenetic modifying enzymes. This review aims to summarize the intergenerational effect of maternal exercise and proposes that gut microbiota-metabolites-epigenetic regulation is an important mechanism by which maternal exercise improves offspring metabolism, which may yield novel targets for the early prevention and intervention of metabolic diseases.

Growing evidence supports changes in the gastrointestinal microbiome over the course of pregnancy may have an impact on the short- and long-term health of both the mother and the child.

Our objective was to explore the association of diet quality, as measured by the Healthy Eating Index (HEI), with the composition and gene ontology (GO) representation of microbial function in the maternal gastrointestinal microbiome during pregnancy.

We conducted a retrospective, observational analysis of n = 185 pregnant participants in the Pregnancy Eating Attributes Study. Maternal dietary intake was assessed in the first trimester using the automated self-administered 24-h recall method, from which the HEI 2015 was calculated. Rectal swabs were obtained in the second trimester and sequenced using the NovaSeq 6000 system shotgun platform. We used unsupervised clustering to identify microbial enterotypes representative of maternal taxa and GO functional term composition. Multivariable linear models were used to identify associations between taxa, functional terms, and food components while controlling for relevant covariates. Multinomial regression was then used to predict enterotype membership based on a participant's HEI food component score.

Those in the high diet quality tertile had a lower early pregnancy BMI [mean (M) = 23.48 kg/m2, SD = 3.38] compared with the middle (M = 27.35, SD = 6.01) and low (M = 27.49, SD = 6.99) diet quality tertiles (P < 0.01). There were no statistically significant associations between the HEI components or the total HEI score and the 4 alpha diversity measures. Differences in taxa and GO term enterotypes were found in participants with, but not limited to, a higher saturated fat component score (β = 1.35, P = 0.01), added sugar HEI component (β = 0.07, P < 0.001), and higher total dairy score (β = 1.58, P = 0.01).

Specific dietary components are associated with microbial composition and function in the second trimester of pregnancy. These findings provide a foundation for future testable hypotheses.

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD's cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD's impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD's complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.

A maternal diet rich in dietary fiber, such as β-glucan, plays a crucial role in the offspring's acquisition of gut microbiota and the subsequent shaping of its microbiome profile and metabolome. This in turn has been shown to aid in neurodevelopmental processes, including early microglial maturation and immunomodulation via metabolites like short chain fatty acids (SCFAs). This study aimed to investigate the effects of oat β-glucan supplementation, solubilized by citric acid hydrolysis, from gestation to adulthood. Female C57BL/6J mice were orally supplemented with soluble oat β-glucan (ObG) or carboxymethyl cellulose (CMC) via drinking water at 200 mg/kg body weight during breeding while the control group received 50 mg/kg body weight of carboxymethyl cellulose. ObG supplementation increased butyrate production in the guts of both dams and 4-week-old pups, attributing to alterations in the gut microbiota profile. One-week-old pups from the ObG group showed increased neurodevelopmental markers similar to four-week-old pups that also exhibited alterations in serum markers of metabolism and anti-inflammatory cytokines. Notably, at 8 weeks, ObG-supplemented pups exhibited the highest levels of spatial memory and cognition compared to the control and CMC groups. These findings suggest a potential enhancement of neonatal neurodevelopment via shaping of early-life gut microbiome profile, and the subsequent increased later-life cognitive function.

The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.

Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women.

Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.

Hypertensive disorders of pregnancy, including pre-eclampsia, are a leading cause of serious and debilitating complications that affect both the mother and the fetus. Despite the occurrence and the health implications of these disorders there is still relatively limited evidence on the molecular underpinnings of the pathophysiology. An area that has come to the fore with regard to its influence on health and disease is the microbiome. While there are several microbiome niches on and within the body, the distal end of the gut harbors the largest of these impacting on many different systems of the body including the central nervous system, the immune system, and the reproductive system. While the role of the microbiome in hypertensive disorders, including pre-eclampsia, has not been fully elucidated some studies have indicated that several of the symptoms of these disorders are linked to an altered gut microbiome. In this review, we examine both pre-eclampsia and microbiome literature to summarize the current knowledge on whether the microbiome drives the symptoms of pre-eclampsia or if the aberrant microbiome is a consequence of this condition. Despite the paucity of studies, obvious gut microbiome changes have been noted in women with pre-eclampsia and the individual symptoms associated with the condition. Yet further research is required to fully elucidate the role of the microbiome and the significance it plays in the development of the symptoms. Regardless of this, the literature highlights the potential for a microbiome targeted intervention such as dietary changes or prebiotic and probiotics to reduce the impact of some aspects of these disorders.

Trimethylamine-N-oxide (TMAO) is a common intestinal metabolite. The Choline in the nutrient forms TMA under the action of the gut microbiota, which passes through the liver and eventually forms TMAO. Initial studies of TMAO focused on cardiovascular disease, but as research progressed, TAMO's effects were found to be multisystem and closely related to the development of neurological diseases. Intestinal tract is the organ with the largest concentration of bacteria in human body, and the composition and metabolism of gut microbiota affect human health. As a two-way communication axis connecting the central nervous system and the gastrointestinal tract, the brain-gut axis provides the structural basis for TMAO to play its role. This article will review the correlation between TMA/TMAO and neurological diseases in order to find new directions and new targets for the treatment of neurological diseases.

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.

Maternal obesity increases the risk of obesity and metabolic disorders (MDs) in offspring, which can be mediated by the gut microbiota. Phlorizin (PHZ) can improve gut dysbiosis and positively affect host health; however, its transgenerational metabolic benefits remain largely unclear. This study aimed to investigate the potential of maternal PHZ intake in attenuating the adverse impacts of a maternal high-fat diet on obesity-related MDs in dams and offspring. The results showed that maternal PHZ reduced HFD-induced body weight gain and fat accumulation and improved glucose intolerance and abnormal lipid profiles in both dams and offspring. PHZ improved gut dysbiosis by promoting expansion of SCFA-producing bacteria, Akkermansia and Blautia, while inhibiting LPS-producing and pro-inflammatory bacteria, resulting in significantly increased fecal SCFAs, especially butyric acid, and reduced serum lipopolysaccharide levels and intestinal inflammation. PHZ also promoted intestinal GLP-1/2 secretion and intestinal development and enhanced gut barrier function by activating G protein-coupled receptor 43 (GPR43) in the offspring. Antibiotic-treated mice receiving FMT from PHZ-regulated offspring could attenuate MDs induced by receiving FMT from HFD offspring through the gut microbiota to activate the GPR43 pathway. It can be regarded as a promising functional food ingredient for preventing intergenerational transmission of MDs and breaking the obesity cycle.

Microbiota in pregnant time is vital to healthy of pregnant women and their offspring. However, few study evaluate the composition of the microbiota of health pregnancy, placenta and their newborns at different stages and the origin of the placental microbiota. Samples were obtained from a total of 31 pregnant individuals and their offspring, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition and variation of them. We found that the microbiota of pregnant individuals changes in the third trimester. The placental microbiota has its own specific dominant microbiota. The placental microbiota is correlated with the pregnancy microbiota in the gut and vagina at 32-34 weeks but not at full term. The gut microbiota in newborns changes over the first 14 days.

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, preeclampsia, preterm birth, and mood disorders. However, the effects of high inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored.

To use a systems-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy.

Forty-nine pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundance with respect to DII score were identified, and microbial metabolic potential was predicted using PICRUSt2.

Inflammatory diets were associated with decreased vitamin and mineral intake and dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism and multi drug efflux systems in pregnant individuals with increased DII scores.

Dietary inflammatory potential was associated with a reduction in the consumption of vitamins & minerals and predicted gut microbiota metabolic dysregulation.

Mammalian pregnancy is characterized by a well-known suite of physiological changes that support fetal growth and development, thereby positively affecting both maternal and offspring fitness. However, mothers also experience trade-offs between current and future maternal reproductive success, and maternal responses to these trade-offs can result in mother-offspring fitness conflicts. Knowledge of the mechanisms through which these trade-offs operate, as well as the contexts in which they operate, is critical for understanding the evolution of reproduction. Historically, hormonal changes during pregnancy have been thought to play a pivotal role in these conflicts since they directly and indirectly influence maternal metabolism, immunity, fetal growth and other aspects of offspring development. However, recent research suggests that gut microbiota may also play an important role. Here, we create a foundation for exploring this role by constructing a mechanistic model linking changes in maternal hormones, immunity and metabolism during pregnancy to changes in the gut microbiota. We posit that marked changes in hormones alter maternal gut microbiome composition and function both directly and indirectly via impacts on the immune system. The gut microbiota then feeds back to influence maternal immunity and metabolism. We posit that these dynamics are likely to be involved in mediating maternal and offspring fitness as well as trade-offs in different aspects of maternal and offspring health and fitness during pregnancy. We also predict that the interactions we describe are likely to vary across populations in response to maternal environments. Moving forward, empirical studies that combine microbial functional data and maternal physiological data with health and fitness outcomes for both mothers and infants will allow us to test the evolutionary and fitness implications of the gestational microbiota, enriching our understanding of the ecology and evolution of reproductive physiology.

Pregnancy is a finely tuned process, with the health and well-being of the developing fetus determined by the metabolic status and dietary intake of the mother. The maternal gut microbiome is remodeled during pregnancy, and this, coupled with the maternal nutrient intake during gestation shapes the production of metabolites that can cross the placenta and affect fetal development. As posited by the Developmental Origins of Health and Disease Hypothesis, such environmental influences can have major effects on the developing organ systems. When occurring at particularly sensitive gestational time points, these developmental programming events can have long lasting effects on offspring adaptation to the postnatal environment, and major health implications later in life. This review will summarize current knowledge on how pregnancy and maternal dietary intake intrinsically and extrinsically modify maternal gut microbiota composition and metabolite production. Further, we will assess how these factors shape the fetal landscape and ultimately contribute to offspring health. DOHaD, fetal development, metabolites, microbiome, nutrition, pregnancy, short-chain fatty acids.

Lifecourse nutrition encompasses nourishment from early development into parenthood. From preconception and pregnancy to childhood, late adolescence, and reproductive years, life course nutrition explores links between dietary exposures and health outcomes in current and future generations from a public health perspective, usually addressing lifestyle behaviours, reproductive well-being and maternal-child health strategies. However, nutritional factors that play a role in conceiving and sustaining new life might also require a molecular perspective and recognition of critical interactions between specific nutrients and relevant biochemical pathways. The present perspective summarises evidence about the links between diet during periconception and next-generation health and outlines the main metabolic networks involved in nutritional biology of this sensitive time frame.

The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.

Gestational diabetes mellitus should be treated adequately to avoid maternal hyperglycemia-related complications. Previously, probiotic supplements were suggested to improve fasting blood glucose in women with gestational diabetes mellitus. However, a major limitation of previous studies was that preprandial and especially postprandial glucose values, which are important predictors of pregnancy outcomes, were not studied.

This study aimed to examine the effect of a mixture of probiotic strains on maternal glycemic parameters, particularly preprandial and postprandial glucose values and pregnancy outcomes among women with gestational diabetes mellitus.

A multicenter prospective randomized, double-blind, placebo-controlled trial was conducted. Women newly diagnosed with gestational diabetes mellitus were randomly allocated into a research group, receiving 2 capsules of oral probiotic formula containing Bifidobacterium bifidum, B lactis, Lactobacillus acidophilus, L paracasei, L rhamnosus, and Streptococcus thermophilus (>6 × 109/capsule), and a control group, receiving a placebo (2 capsules/day) until delivery. Glycemic control was evaluated by daily glucose charts. After 2 weeks, pharmacotherapy was started in case of poor glycemic control. The primary outcomes were the rate of women requiring medications for glycemic control and mean daily glucose charts after 2 weeks of treatment with the study products.

Forty-one and 44 women were analyzed in the treatment and placebo cohorts, respectively. Mean daily glucose during the first 2 weeks in the probiotics and placebo groups was 99.7±7.9 and 98.0±9.3 mg/dL, respectively (P=.35). The rate of women needing pharmacotherapy because of poor glycemic control after 2 weeks of treatment in the probiotics and placebo groups was 24 (59%) and 18 (41%), respectively (P=.10). Mean preprandial and postprandial glucose levels throughout the study period were similar between the groups (P>.05). There were no differences in maternal and neonatal outcomes, including birthweight and adverse effect profile between the groups.

The oral probiotic product tested in this study did not affect glycemic control of women with gestational diabetes mellitus.

Autism spectrum disorders (ASD) are highly heritable, heterogeneous neurodevelopmental disorders characterized by clinical presentation of atypical social, communicative, and repetitive behaviors. Over the past 25 years, hundreds of ASD risk genes have been identified. Many converge on key molecular pathways, from translational control to those regulating synaptic structure and function. Despite these advances, therapeutic approaches remain elusive. Emerging data unearthing the relationship between genetics, microbes, and immunity in ASD suggest an integrative physiology approach could be paramount to delivering therapeutic breakthroughs. Indeed, the advent of large-scale multi-OMIC data acquisition, analysis, and interpretation is yielding an increasingly mechanistic understanding of ASD and underlying risk factors, revealing how genetic susceptibility interacts with microbial genetics, metabolism, epigenetic (re)programming, and immunity to influence neurodevelopment and behavioral outcomes. It is now possible to foresee exciting advancements in the treatment of some forms of ASD that could markedly improve quality of life and productivity for autistic individuals. Here, we highlight recent work revealing how gene X maternal exposome interactions influence risk for ASD, with emphasis on the intrauterine environment and fetal neurodevelopment, host-microbe interactions, and the evolving therapeutic landscape for ASD.

The community structure of gut microbiota changes during pregnancy, which also affects the synthesis of short-chain fatty acids (SCFAs). However, the distribution of gut microbiota composition and metabolite SCFA levels are poorly understood in women undergoing assisted reproductive technology (ART).

To evaluate the changes in gut microbiota composition and metabolic SCFAs in women who received assisted reproduction treatment.

Sixty-three pregnant women with spontaneous pregnancy (SP) and nine with ART pregnancy were recruited to provide fecal samples. Gut microbiota abundance and SCFA levels were determined by 16S ribosomal RNA (rRNA) gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS).

The ART group showed decreased alpha diversity (the species richness or evenness in a sample). The principal coordinates analysis (a method of analysing beta diversity) showed significant difference in gut microbiota between the ART group versus the SP group (unweighted UniFrac distance, R 2 =0.04, P =0.003). Proteobacteria , Blautia and Escherichia-Shigella were enriched in the ART group, whereas the relative abundance of beneficial intestinal bacteria Faecalibacterium was lower than in the SP group. Different modes of conception were associated with several SCFAs (valeric acid (r =-0.280; P =0.017); isocaproic acid (r =-0.330; P =0.005); caproic acid (r =-0.336; P =0.004)). Significantly different SCFAs between the two groups were synchronously associated with the differential gut microbiota.

The diversity and abundance of gut microbiota and the levels of SCFAs in women undergoing ART decreased.

The application of ART shaped the microbial composition and metabolism, which may provide critical information for understanding the biological changes that occur in women with assisted reproduction.

Microbiome differential abundance analysis methods for two groups are well-established in the literature. However, many microbiome studies involve more than two groups, sometimes even ordered groups such as stages of a disease, and require different types of comparison. Standard pairwise comparisons are inefficient in terms of power and false discovery rates. In this Article, we propose a general framework, ANCOM-BC2, for performing a wide range of multigroup analyses with covariate adjustments and repeated measures. We illustrate our methodology through two real datasets. The first example explores the effects of aridity on the soil microbiome, and the second example investigates the effects of surgical interventions on the microbiome of patients with inflammatory bowel disease.

Adequate nutrient supply is crucial for the proper development of the embryo. Although nutrient supply is determined by maternal diet, the gut microbiota also influences nutrient availability. While currently there is no cure for neural tube defects (NTDs), their prevention is largely amenable to maternal folic acid and inositol supplementation. The gut microbiota also contributes to the production of these nutrients, which are absorbed by the host, but its role in this context remains largely unexplored. In this study, we performed a functional and morphological analysis of the intestinal tract of loop-tail mice (Vangl2 mutants), a mouse model of folate/inositol-resistant NTDs. In addition, we investigated the changes in gut microbiota using 16S rRNA gene sequencing regarding (1) the host genotype; (2) the sample source for metagenomics analysis; (3) the pregnancy status in the gestational window of neural tube closure; (4) folic acid and (5) D-chiro-inositol supplementation. We observed that Vangl2+/Lp mice showed no apparent changes in gastrointestinal transit time or fecal output, yet exhibited increased intestinal length and cecal weight and gut dysbiosis. Moreover, our results showed that the mice supplemented with folic acid and D-chiro-inositol had significant changes in their microbiota composition, which are changes that could have implications for nutrient absorption.

Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.

With the rising number of cases of non-vaginal delivery worldwide, scientists have been concerned about the influence of the different delivery modes on maternal and neonatal microbiomes. Although the birth rate trend is decreasing rapidly in Taiwan, more than 30 percent of newborns are delivered by caesarean section every year. However, it remains unclear whether the different delivery modes could have a certain impact on the postpartum maternal microbiome and whether it affects the mother-to-newborn vertical transmission of bacteria at birth.

To address this, we recruited 30 mother-newborn pairs to participate in this study, including 23 pairs of vaginal delivery (VD) and seven pairs of caesarean section (CS). We here investigate the development of the maternal prenatal and postnatal microbiomes across multiple body habitats. Moreover, we also explore the early acquisition of neonatal gut microbiome through a vertical multi-body site microbiome analysis.

The results indicate that no matter the delivery mode, it only slightly affects the maternal microbiome in multiple body habitats from pregnancy to postpartum. On the other hand, about 95% of species in the meconium microbiome were derived from one of the maternal body habitats; notably, the infants born by caesarean section acquire bacterial communities resembling their mother's oral microbiome. Consequently, the delivery modes play a crucial role in the initial colonization of the neonatal gut microbiome, potentially impacting children's health and development.

Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.

Maternal microbiota forms the first infant gut microbial inoculum, and perinatal factors (diet and use of antibiotics during pregnancy) and/or neonatal factors, like intra partum antibiotics, gestational age and mode of delivery, may influence microbial colonization. After birth, when the principal colonization occurs, the microbial diversity increases and converges toward a stable adult-like microbiota by the end of the first 3-5 years of life. However, during the early life, gut microbiota can be disrupted by other postnatal factors like mode of infant feeding, antibiotic usage, and various environmental factors generating a state of dysbiosis. Gut dysbiosis have been reported to increase the risk of necrotizing enterocolitis and some chronic diseases later in life, such as obesity, diabetes, cancer, allergies, and asthma. Therefore, understanding the impact of a correct maternal-to-infant microbial transfer and a good infant early colonization and maturation throughout life would reduce the risk of disease in early and late life. This paper reviews the published evidence on early-life gut microbiota development, as well as the different factors influencing its evolution before, at, and after birth, focusing on diet and nutrition during pregnancy and in the first months of life.

It is clear that the gastrointestinal tract influences metabolism and immune function. Most studies to date have used male test subjects, with a focus on effects of obesity and dietary challenges. Despite significant physiological maternal adaptations that occur across gestation, relatively few studies have examined pregnancy-related gut function. Moreover, it remains unknown how pregnancy and diet can interact to alter intestinal barrier function. In this study, we investigated the impacts of pregnancy and adiposity on maternal intestinal epithelium morphology, in vivo intestinal permeability, and peripheral blood immunophenotype, using control (CTL) and high-fat (HF) fed non-pregnant female mice and pregnant mice at mid- (embryonic day (E)14.5) and late (E18.5) gestation. We found that small intestine length increased between non-pregnant mice and dams at late-gestation, but ileum villus length, and ileum and colon crypt depths and goblet cell numbers remained similar. Compared to CTL-fed mice, HF-fed mice had reduced small intestine length, ileum crypt depth and villus length. Goblet cell numbers were only consistently reduced in HF-fed non-pregnant mice. Pregnancy increased in vivo gut permeability, with a greater effect at mid- versus late-gestation. Non-pregnant HF-fed mice had greater gut permeability, and permeability was also increased in HF-fed pregnant dams at mid but not late-gestation. The impaired maternal gut barrier in HF-fed dams at mid-gestation coincided with changes in maternal blood and bone marrow immune cell composition, including an expansion of circulating inflammatory Ly6Chigh monocytes. In summary, pregnancy has temporal effects on maternal intestinal structure and barrier function, and on peripheral immunophenotype, which are further modified by HF diet-induced maternal adiposity. Maternal adaptations in pregnancy are thus vulnerable to excess maternal adiposity, which may both affect maternal and child health.

Preeclampsia (PE) is a common pregnancy-related disorder characterized by disrupted maternal-fetal immune tolerance, involving diffuse inflammatory responses and vascular endothelial damage. Alterations in the gut microbiota (GM) during pregnancy can affect intestinal barrier function and immune balance.

This comprehensive review aims to investigate the potential role of short-chain fatty acids (SCFAs), essential metabolites produced by the GM, in the development of PE. The purpose is to examine their impact on colonic peripheral regulatory T (Treg) cells, the pathogenic potential of antigen-specific helper T (Th) cells, and the inflammatory pathways associated with immune homeostasis.

An increasing body of evidence suggests that dysbiosis in the GM can lead to alterations in SCFA levels, which may significantly contribute to the development of PE. SCFAs enhance the number and function of colonic Treg cells, mitigate the pathogenic potential of GM-specific Th cells, and inhibit inflammatory progression, thereby maintaining immune homeostasis. These insights highlight the potential significance of GM dysregulation and SCFAs produced by GM in the pathogenesis of PE. While the exact causes of PE remain elusive, and definitive clinical treatments are lacking, the GM and SCFAs present promising avenues for future clinical applications related to PE, offering a novel approach for prophylaxis and therapy.

Postpartum depression (PPD) is a challenging psychological disorder faced by 10-30% of mothers across the globe. In India, it occurs among 22% of mothers. Its aetiology and pathophysiology aren't fully understood as of today but multiple theories on the interplay of hormones, neurotransmitters, genetics, epigenetics, nutrients, socio-environmental factors, etc. exist. Nutrients are not only essential for the synthesis of neurotransmitters, but they may also indirectly influence genomic pathways that methylate DNA, and there is evidence for molecular associations between nutritional quality and psychological well-being. Increased behavioural disorders have been attributed to macro- and micronutrient deficiencies, and dietary supplementation has been effective in treating several neuropsychiatric illnesses. Nutritional deficiencies occur frequently in women, especially during pregnancy and breastfeeding. The aim of this study was to perform a comprehensive literature review of evidence-based research in order to identify, gather and summarize existing knowledge on PPD's aetiology, pathophysiology, and the role of nutrients in its prevention as well as management. The possible mechanisms of action of nutrients are also presented here. Study findings show that the risk of depression increases when omega-3 fatty acid levels are low. Both fish oil and folic acid supplements have been used to effectively treat depression. Antidepressant efficacy is lowered by folate insufficiency. Folate, vitamin B12, iron, etc. deficiencies are more prevalent in depressed people than in non-depressed people. Serum cholesterol levels and plasma tryptophan levels are found to be inversely correlated with PPD. Serum vitamin D levels were associated inversely with perinatal depression. These findings highlight the importance of adequate nutrition in the antepartum period. Given that nutritional therapies can be affordable, safe, simple to use, and are typically well-accepted by patients, more focus should be placed on dietary variables in PPD.

Gestational diabetes mellitus (GDM) is an intractable issue that negatively impacts the quality of pregnancy. The incidence of GDM is on the rise, becoming a major health burden for both mothers and children. However, the specific etiology and pathophysiology of GDM remain unknown. Recently, the importance of gut microbiota and related metabolic molecules has gained prominence. Studies have indicated that women with GDM have significantly distinct gut microbiota and gut metabolites than healthy pregnant women. Given that the metabolic pathways of gut flora and related metabolites have a substantial impact on inflammation, insulin signaling, glucose, and lipid metabolism, and so on, gut microbiota or its metabolites, such as short-chain fatty acids, may play a significant role in both pathogenesis and progression of GDM. Whereas the role of intestinal flora during pregnancy is still in its infancy, this review aims to summarize the effects and mechanisms of gut microbiota and related metabolic molecules involved in GDM, thus providing potential intervention targets.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has been associated with an increased risk of obesity and diabetes in the offspring. Pregnancy is accompanied by tightly regulated changes in the endocrine, metabolic, immune, and microbial systems, and deviations from these changes can alter the mother's metabolism resulting in adverse pregnancy outcomes and a negative impact on the health of her infant. Maternal microbiomes are significant drivers of mother and child health outcomes, and many microbial metabolites are likely to influence the host health. This review discusses the current understanding of how the microbiota and microbial metabolites may contribute to the development of GDM and how GDM-associated changes in the maternal microbiome can affect infant's health. We also describe microbiota-based interventions that aim to improve metabolic health and outline future directions for precision medicine research in this emerging field.

Vaginal and rectal specimens were obtained from cycling, pregnant, and nursing rhesus monkeys to assess pregnancy-related changes in the commensal bacteria in their reproductive and intestinal tracts. Using 16S rRNA gene amplicon sequencing, significant differences were found only in the vagina at mid-gestation, not in the hindgut. To verify the apparent stability in gut bacterial composition at mid-gestation, the experiment was repeated with additional monkeys, and similar results were found with both 16S rRNA gene amplicon and metagenomic sequencing. A follow-up study investigated if bacterial changes in the hindgut might occur later in pregnancy. Gravid females were assessed closer to term and compared to nonpregnant females. By late pregnancy, significant differences in bacterial composition, including an increased abundance of 4 species of Lactobacillus and Bifidobacterium adolescentis, were detected, but without a shift in the overall community structure. Progesterone levels were assessed as a possible hormone mediator of bacterial change. The relative abundance of only some taxa (e.g., Bifidobacteriaceae) were specifically associated with progesterone. In summary, pregnancy changes the microbial profiles in monkeys, but the bacterial diversity in their lower reproductive tract is different from women, and the composition of their intestinal symbionts remains stable until late gestation when several Firmicutes become more prominent.

Microbiome differential abundance analysis methods for a pair of groups are well established in the literature. However, many microbiome studies involve multiple groups, sometimes even ordered groups, such as stages of a disease, and require different types of comparisons. Standard pairwise comparisons are not only inefficient in terms of power and false discovery rates, but they may not address the scientific question of interest. In this paper, we propose a general framework for performing a wide range of multi-group analyses with covariate adjustments and repeated measures. We demonstrate the effectiveness of our methodology through two real data sets. The first example explores the effects of aridity on the soil microbiome, and the second example investigates the effects of surgical interventions on the microbiome of IBD patients.