A model of early-life interactions between the gut microbiome and adaptive immunity provides insights into the ontogeny of immune tolerance.

To achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such 'immune education' unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in humans during early life.

Polygenic Risk Scores for Type 2 Diabetes in the Swiss HIV Cohort Study.

Background: Type 2 diabetes (T2D) is among the most frequent comorbidities in people with HIV (PWH) and occurs more often in PWH than in people without HIV. Polygenic risk scores (PRS) can be used to summarize the genetic risk for T2D, but it is unknown to what extent HIV-specific factors impact on or interact with genetic risk factors.

Methods: We performed a case control study using incidence density sampling to match participants with T2D to controls within the Swiss HIV Cohort Study (mean age 51.

Getting ahead of human-associated microbial decline in Africa: the urgency of sampling in light of epidemiological transition.

Evidence is growing that human-associated early-life microbial diversity modulates health over the long term, via effects in the infant termed 'immune and metabolic education'. Documenting high microbial diversity contexts, such as in Africa, thus, has rich potential for understanding this aspect of the landscape of health. Yet, change on the continent is occurring rapidly, and microbial communities are shifting as behaviors and diets are altered, and antibiotic use expands; we may be losing the opportunity to obtain relevant data.

Computational and in vitro evaluation of probiotic treatments for nasal decolonization.

Despite the rising challenge of antibiotic resistance, current approaches to eradicate nasal pathobionts and rely on antibacterials. An alternative is the artificial inoculation of commensal bacteria, i.e.

Transcriptional profile of infection in people living with HIV.

In people with HIV-1 (PWH), (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals.

Antibodies in breast milk: Pro-bodies designed for healthy newborn development.

This manuscript sheds light on the impact of maternal breast milk antibodies on infant health. Milk antibodies prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment. While the transfer of IgG across the placenta ceases at birth, milk antibodies are continuously replenished by the maternal immune system.

Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications.

Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender.

Understanding the Decline of Incident, Active Tuberculosis in People With Human Immunodeficiency Virus in Switzerland.

Background: People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear.

Methods: We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS).

Hosts, microbiomes, and the evolution of critical windows.

The absence of microbial exposure early in life leaves individuals vulnerable to immune overreaction later in life, manifesting as immunopathology, autoimmunity, or allergies. A key factor is thought to be a "critical window" during which the host's immune system can "learn" tolerance, and beyond which learning is no longer possible. Animal models indicate that many mechanisms have evolved to enable critical windows, and that their time limits are distinct and consistent.

Impact of Latent Tuberculosis on Diabetes.

While an increased risk of active and latent tuberculosis infection (LTBI) in people with type-2 diabetes (DM) has been demonstrated, it is less well characterized whether LTBI is associated with an increased risk of developing DM. We investigated the link between LTBI and DM in people living with HIV in the Swiss HIV Cohort Study via time-dependent Cox proportional hazards models. We found that LTBI significantly increased the risk of developing DM (HR = 1.

Comparing treatment strategies to reduce antibiotic resistance in an in vitro epidemiological setting.

The rapid rise of antibiotic resistance, combined with the increasing cost and difficulties to develop new antibiotics, calls for treatment strategies that enable more sustainable antibiotic use. The development of such strategies, however, is impeded by the lack of suitable experimental approaches that allow testing their effects under realistic epidemiological conditions. Here, we present an approach to compare the effect of alternative multidrug treatment strategies in vitro using a robotic liquid-handling platform.

Assessing the potential impact of transmission during prolonged viral shedding on the effect of lockdown relaxation on COVID-19.

A key parameter in epidemiological modeling which characterizes the spread of an infectious disease is the generation time, or more generally the distribution of infectiousness as a function of time since infection. There is increasing evidence supporting a prolonged viral shedding window for COVID-19, but the transmissibility in this phase is unclear. Based on this, we develop a generalized Susceptible-Exposed-Infected-Resistant (SEIR) model including an additional compartment of chronically infected individuals who can stay infectious for a longer duration than the reported generation time, but with infectivity reduced to varying degrees.

Quantifying the impact of treatment history on plasmid-mediated resistance evolution in human gut microbiota.

To understand how antibiotic use affects the risk of a resistant infection, we present a computational model of the population dynamics of gut microbiota including antibiotic resistance-conferring plasmids. We then describe how this model is parameterized based on published microbiota data. Finally, we investigate how treatment history affects the prevalence of resistance among opportunistic enterobacterial pathogens.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug.