The importance of the gut in regulating the brain–body immune axis is becoming increasingly evident. Interestingly, the brain and gut share many common signaling molecules, with serotonin being one of the most notable. In fact, the gut is the primary source of serotonin in the body. However, studying serotonin dynamics in a human-specific context remains a challenge. Human stem cell-derived models provide a promising avenue for studying signal transmission in well-controlled, in vitro environments. In this study, we report the first fast-scan cyclic voltammetry (FSCV) measurements of serotonin signaling in a newly developed enterochromaffin cell (ECC)-enriched gut organoid model. First, we characterize the stem cell-derived gut organoids and confirm they are enriched with ECCs, the key cell type responsible for producing and releasing serotonin in the gut. We then optimize an in vitro buffer that maintains cell viability while supporting FSCV measurements. Using this system, we detect spontaneous release events, which increase in frequency and amplitude following stimulation with forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX). Finally, we confirm the identity of the signal as serotonin using a selective serotonin reuptake inhibitor (SSRI), which significantly delayed the reuptake profile. Our study introduces the first real-time measurement of serotonin signaling in a human-derived gut model. We believe this system will be essential for future research on serotonin’s role in the gut and for potential novel drug target identification.

This study identifies parallel gut–brain pathways that fine-tune feeding. Distinct brainstem neurons and visceral afferents either sense esophageal stretch to regulate eating speed or detect gut nutri...

Orthogonal murine models demonstrate the bioactivity and neuronal targets of a GLP-1/leptin coagonist in relation to food intake and body weight.

The functional role of peripheral GIPR action in weight loss is yet to be fully defined in a preclinical setting. Here, Yu et al. propose a mechanism whereby inducible activation of GIPR in adipocytes promotes energy wasting through futile calcium cycling, triggering profound weight loss in the obese state.

Orthogonal murine models demonstrate the bioactivity and neuronal targets of a GLP-1/leptin coagonist in relation to food intake and body weight.

The U.K. will soon offer Eli Lilly's Mounjaro for people with obesity — but only to a small share of those medically eligible, and alongside a specialized diet.

The advent of droplet-based single-cell RNA-sequencing (scRNA-seq) has dramatically increased data throughput, enabling the release of a diverse array of tissue cell atlases to the public. However, we...

Methods to culture intestinal stem cells (ISCs) are often limited by undefined culture conditions arising from the use of basement membrane extracts or feeder cell layers. Here, the authors propose a ...

Identification of an LGR5 as a marker for a tripotent stem/progenitor cell of the human fetal pancreas. Organoids derived from single LGR5+ cells are capable of long-term expansion in vitro and genera...

This study identifies parallel gut–brain pathways that fine-tune feeding. Distinct brainstem neurons and visceral afferents either sense esophageal stretch to regulate eating speed or detect gut nutri...

Nature Metabolism - Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.

Human brain organoids are powerful in vitro models for brain development and disease. However, their variability can complicate use in biomedical research and drug discovery. Both the specific protoco...

Intestinal tuft cells are epithelial sentinels that trigger host defense upon detection of parasite-derived compounds. While representing interesting targets for immunomodulatory therapies in inflamma...

Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we ...

To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, se...

The brain senses changes to the internal state of the body, eliciting responses that maintain homeostasis. Alhadeff and Yapici provide an overview of this process, termed interoception, with a particu...

Soils from 30 grasslands across Europe were subjected to 4 contrasting extreme climatic events under drought, flood, freezing and heat conditions, with the results suggesting that soil microbiomes fro...

In 2015, introduction of a disease staging system offered a framework for benchmarking progression to clinical type 1 diabetes. This model, based on islet autoantibodies (stage 1) and dysglycaemia (st...

Dual incretin agonists are among the most effective pharmaceutical treatments for obesity and type 2 diabetes to date. Such therapeutics can target tw…

Steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus play key roles in the regulation of food intake, body weight and glucose metabol…

Abstract. The Natural Products Atlas is a database of microbially derived natural products that contains structures, producing organism taxonomy, biosynthe

International Journal of Obesity - Plasma concentration of gastrointestinal hormones and subjective appetite ratings after diet or bariatric surgery: 1-year results from the DISGAP study

Gut microbes are known to modulate stress responsivity and behavior. Tofani et al. demonstrate that such modulations occur via the circadian system. The oscillations in gut microbiota composition regu...

The insulin inhibitory receptor (inceptor) is found to bind to insulin and to regulate insulin stores by directing proinsulin and insulin towards lysosomal degradation.

This Viewpoint discusses the health benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); summarizes the clinical, policy, and equity implications of GLP-1 RA discontinuation; and calls f...

Aims/hypothesis We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-tr...