You've got male: Sex and the microbiota-gut-brain axis across the lifespan.

Individuals who are minoritized as a result of race, sexual identity, gender, or socioeconomic status experience a higher prevalence of many diseases. Understanding the biological processes that cause and maintain these socially driven health inequities is essential for addressing them. The gut microbiome is strongly shaped by host environments and affects host metabolic, immune, and neuroendocrine functions, making it an important pathway by which differences in experiences caused by social, political, and economic forces could contribute to health inequities. Nevertheless, few studies have directly integrated the gut microbiome into investigations of health inequities. Here, we argue that accounting for host-gut microbe interactions will improve understanding and management of health inequities, and that health policy must begin to consider the microbiome as an important pathway linking environments to population health.

https://www.pnas.org/content/pnas/118/25/e2017947118.full.pdf

The human gut microbiome and health inequities.

Although antibiotics confer significant health benefits in treating or preventing bacterial infections, an accumulating wealth of evidence illustrates their detrimental effect on host-microbiota homeostasis, posing a serious menace to the global public health. In recent years, it is becoming evident that infants, who are subjected to frequent antibiotic exposures due to their vulnerability to infection, reflect increased susceptibility to a wide spectrum of diseases, including infection, in later life. Antibiotics induce perturbations of the microbiota or dysbiosis, which in turn alters the host immune responses against pathogens. In comparison with adults, antibiotic treatments in infants have disproportionate consequences because the infant microbiota represents an evolving system that is unstable and immature until 2-3 years of age. However, relatively less knowledge is available on how antibiotics affect the infant microbiota and immunity. In this review article, we focus on how antibiotic treatment regimens influence the infant innate and adaptive immunity to pathogens in humans and animal models, and make the host susceptible to infections in later life. There is a critical need to better understand the effect of antibiotics on infant immune function, which may have implications for developing effective prophylactics and therapeutics against diseases in infants and adults.

/pdf/the-dark-side-of-antibiotics-adverse-effects-on-the-infant-56bdl7b57w.pdf

The Dark Side of Antibiotics: Adverse Effects on the Infant Immune Defense Against Infection.

Allergic diseases are highly complex with respect to pathogenesis, inflammation, and response to treatment. Current efforts for allergic disease diagnosis have focused on clinical evidence as a binary outcome. Although outcome status based on clinical phenotypes (observable characteristics) is convenient and inexpensive to measure in large studies, it does not adequately provide insight into the complex molecular determinants of allergic disease. Individuals with similar clinical diagnoses do not necessarily have similar disease etiologies, natural histories, or responses to treatment. This heterogeneity contributes to the ineffective response to treatment leading to an annual estimated cost of $350 billion in the USA alone. There has been a recent focus to deconvolute the clinical heterogeneity of allergic diseases into specific endotypes using molecular and omics approaches. Endotypes are a means to classify patients based on the underlying pathophysiological mechanisms involving distinct functions or treatment response. The advent of high-throughput molecular omics, immunophenotyping, and bioinformatics methods including machine learning algorithms is facilitating the development of endotype-based diagnosis. As we move to the next decade, we should truly start treating clinical endotypes not clinical phenotype. This review highlights current efforts taking place to improve allergic disease endotyping via molecular omics profiling, immunophenotyping, and machine learning approaches in the context of precision diagnostics in allergic diseases. Graphical Abstract.

Resolving Clinical Phenotypes into Endotypes in Allergy: Molecular and Omics Approaches.

Society to cell: How child poverty gets “Under the Skin” to influence child development and lifelong health

While the association between early life determinants and the development of the gut microbiome composition in infancy has been widely investigated, a potential persistent influence of early life determinants on the gut microbial community after its stabilization at later childhood remains largely unknown. Therefore, we aimed to identify the association between several early life determinants and the gut microbiome composition in six-year-old children from the LISA birth cohort. A total number of 166 fecal samples were analyzed using 16S rRNA gene-based barcoding to assess bacterial diversity pattern. The bacterial profiles were investigated for their association with maternal smoking during pregnancy, mode of delivery, breastfeeding, antibiotic treatment between one and two years of age, gender and socioeconomic status (SES). While alpha and beta diversity of the infants’ gut microbiome remained unaffected, amplicon sequence variants (ASVs) annotated to Firmicutes and Actinobacteria responded to early life determinants, mostly to feeding practice and antibiotics use. ASVs associated to Bacteriodetes remained unaffected. Our findings indicate that early life determinants could have a long-term sustainable effect on the gut microflora of six-year-old children, however, associations with early life determinates are weaker than reported for infants.

/pdf/early-life-determinants-induce-sustainable-changes-in-the-4jdbqnfs4v.pdf

Early life determinants induce sustainable changes in the gut microbiome of six-year-old children.

ABSTRACT Despite a short history since its first isolation, Akkermansia muciniphila has been extensively studied in relation to its effects on human metabolism. A recent human intervention study also demonstrated that the bacterium is safe to use for therapeutic purposes. The best-known effects of A. muciniphila in human health and disease relate to its ability to strengthen gut integrity, modulate insulin resistance, and protect the host from metabolic inflammation. A further molecular mechanism, induction of GLP-1 secretion through ICAM-2 receptor, was recently discovered with the identification of a new bacterial protein produced by A. muciniphila. However, other studies have suggested a detrimental role for A. muciniphila in specific host immune settings. Here, we evaluate the molecular, mechanistic effects of A. muciniphila in host health and suggest some of the missing links to be connected before the organism should be considered as a next-generation biotherapeutic agent.

https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2078619?needAccess=true

Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis. Graphical abstract

https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2078612?needAccess=true

Hyena Kang

Papers

Early life determinants induce sustainable changes in the gut microbiome of six-year-old children.

Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium

Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis