Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy

Many of the immune and metabolic changes occurring during normal pregnancy also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in nonpregnant hosts. Here, to explore their role in pregnancy, we characterized fecal bacteria of 91 pregnant women of varying prepregnancy BMIs and gestational diabetes status and their infants. Similarities between infant-mother microbiotas increased with children's age, and the infant microbiota was unaffected by mother's health status. Gut microbiota changed dramatically from first (T1) to third (T3) trimesters, with vast expansion of diversity between mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced richness. T3 stool showed strongest signs of inflammation and energy loss; however, microbiome gene repertoires were constant between trimesters. When transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Our findings indicate that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy.     

Gut Microbiome in Down Syndrome

Background

Premature aging seriously compromises the health status of Down Syndrome (DS) persons. Since human aging has been associated with a deterioration of the gut microbiota (GM)-host mutualism, here we investigated the composition of GM in DS.

Methods

The observational study presented involved 17 adult DS persons. We characterized the GM structure by 454 pyrosequencing of the V4 region of the 16S rRNA gene. DS microbiome was compared with that of age-matched healthy non-trisomic adults enrolled in the same geographic area.

Results and Conclusions

The dominant GM fraction of DS persons showed an overall mutualistic immune-modulatory layout, comparable to that of healthy controls. This makes GM a possible factor counteracting the genetic determined acceleration of immune senescence in DS persons. However, we also found detectable signatures specific for DS among subdominant GM components, such as the increase of Parasporobacterium and Sutterella. In particular, the abundance of this last microorganism significantly correlated with the Aberrant Behavior Checklist (ABC) total score, allowing us to hypothesize a possible role for this microbial genus in behavioral features in DS.     

Host and Symbiont Jointly Control Gut Microbiota during Complete Metamorphosis

Holometabolous insects undergo a radical anatomical re-organisation during metamorphosis. This poses a developmental challenge: the host must replace the larval gut but at the same time retain symbiotic gut microbes and avoid infection by opportunistic pathogens. By manipulating host immunity and bacterial competitive ability, we study how the host Galleria mellonella and the symbiotic bacterium Enterococcus mundtii interact to manage the composition of the microbiota during metamorphosis. Disenabling one or both symbiotic partners alters the composition of the gut microbiota, which incurs fitness costs: adult hosts with a gut microbiota dominated by pathogens such as Serratia and Staphylococcus die early. Our results reveal an interaction that guarantees the safe passage of the symbiont through metamorphosis and benefits the resulting adult host. Host-symbiont “conspiracies” as described here are almost certainly widespread in holometobolous insects including many disease vectors.     

A New Clarification Method to Visualize Biliary Degeneration During Liver Metamorphosis in Sea Lamprey (Petromyzon marinus)

Biliary atresia is a rare disease of infancy, with an estimated 1 in 15,000 frequency in the southeast United States, but more common in East Asian countries, with a reported frequency of 1 in 5,000 in Taiwan. Although much is known about the management of biliary atresia, its pathogenesis is still elusive. The sea lamprey (Petromyzon marinus) provides a unique opportunity to examine the mechanism and progression of biliary degeneration. Sea lamprey develop through three distinct life stages: larval, parasitic, and adult. During the transition from larvae to parasitic juvenile, sea lamprey undergo metamorphosis with dramatic reorganization and remodeling in external morphology and internal organs. In the liver, the entire biliary system is lost, including the gall bladder and the biliary tree. A newly-developed method called “CLARITY” was modified to clarify the entire liver and the junction with the intestine in metamorphic sea lamprey. The process of biliary degeneration was visualized and discerned during sea lamprey metamorphosis by using laser scanning confocal microscopy. This method provides a powerful tool to study biliary atresia in a unique animal model.     

Diet,Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites

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Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.     

Towards Predictive Models of the Human Gut Microbiome

The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the state of the art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model.     

Changes in Water Content during Metamorphosis of the Housefly,Musca domestica

The synthesis of ( – )-cis-neocnidilide (1), a stereoisomer of neocnidilide (2) having inhibiting activity against mycotoxin-producing fungi, is described. ( ±)-(E)-1,3-Nonadien-5-ol was kinetically resolved to give (S)-13, which was converted to (S)-triene ester 8. The intramolecular Diels-Alder reaction of 8 afforded a mixture of 12 and 10. The dihydro derivative 14, obtained by catalytic hydrogenation of 12, was transformed via trimethylsilylketene acetal into α-bromolactone 19, which upon treatment with DBU in toluene, gave rise to ( – )-cis-neocnidilide (1).     

东北七鳃鳗肠道应答气单胞菌免疫刺激相关蛋白的鉴定

动物肠道中寄生的微生物与宿主的营养、免疫及防御功能密切相关。本研究在东北七鳃鳗肠道中分离获得一株优势细菌,并鉴定为气单胞菌属（Aeromonads sp.）。建立了荧光定量PCR快速检测气单胞菌拷贝数的方法,经poly(I∶C)刺激后,气单胞菌数量下降115倍。因此,该肠道气单胞菌被认为是七鳃鳗肠道适应性免疫系统进化的关键菌群之一。为了进一步分析气单胞菌对东北七鳃鳗肠道适应性免疫影响的分子机制,将分离菌株腹腔注射七鳃鳗,利用双向电泳技术鉴定了七鳃鳗肠道应答气单胞菌免疫刺激的相关蛋白。共鉴定19个差异表达蛋白质,其中12个蛋白质表达上调,5个蛋白质表达下调,1个蛋白质刺激后消失,1个新增蛋白质,并对蛋白质功能进行分类。七鳃鳗肠道应答气单胞菌免疫刺激的差异表达蛋白分别参与了七鳃鳗适应性免疫调控、信号转导及能量代谢等。该研究可拓宽对七鳃鳗免疫研究的途径,为深入探讨适应性免疫系统发育提供理论基础和新的研究思路。     

Interplay of Human Gut Microbiome in Health and Wellness

Indian Journal of Microbiology - The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the...     

Effects of Heat Stress on Gut Microbiome in Rats

Gut microbiome, as the largest and most important micro-ecosystem, plays a critical role in health. The purpose of this study was to evaluate whether heat stress modulates the composition and diversity of the gut microbiome in rats. The heat stress model was prepared in rats with the heating temperature maintained at 35–38°C. Cecum contents were collected after heat stress for 3 h and days 1, 3 and 7. Total DNA was extracted for 16 S rRNA sequencing and analysis of intestinal microbiome composition and diversity. The study showed that the composition of the intestinal microbiome of heat stress group was changed. And the heat stress modulated key phylotypes of gut microbiota at the level of phylum and genus. In particular, the genus of Lactobacillus and Bacteroides were significantly reduced, whereas the Oscillospira and Clostridium were increased by heat stress. Meanwhile, the rats under the heat stress encountered the change in carbohydrate metabolism, amino acid metabolism, and membrane transport to defense against stress. Taken together, the composition and structure of gut microbiome were affected by heat stress and some key phylotypes were also significantly altered. We conclude that the heat stress could impact multiple biological functions, via altering the gut microbiome.     

Focus: Microbiome: Integrative Therapies in Anxiety Treatment with Special Emphasis on the Gut Microbiome

Over the past decade, research has shown that diet and gut health affects symptoms expressed in stress related disorders, depression, and anxiety through changes in the gut microbiota. Psycho-behavioral function and somatic health interaction have often been ignored in health care with resulting deficits in treatment quality and outcomes. While mental health care requires the professional training in counseling, psychotherapy and psychiatry, complimentary therapeutic strategies, such as attention to a nutritional and diverse diet and supplementation of probiotic foods, may be integrated alongside psychotherapy treatment models. Development of these alternative strategies is predicated on experimental evidence and diligent research on the biology of stress, fear, anxiety-related behaviors, and the gut-brain connection. This article provides a brief overview on biological markers of anxiety and the expanding nutritional literature relating to brain health and mental disorders. A case study demonstrates an example of a biopsychosocial approach integrating cognitive psychotherapy, dietary changes, and mindfulness activities, in treating symptoms of anxiety. This case study shows a possible treatment protocol to explore the efficacy of targeting the gut-brain-axis that may be used as an impetus for future controlled studies.     

Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome

We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.     

Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi‐omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome‐targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host–microbiome interactions. Combining these functional ‐omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi‐omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.