Studies of the putative functional relationships between the gut microbiota and host cardiometabolic diseases (CMDs), including atherosclerosis, diabetes, and metabolic dysfunction-associated steatohepatitis (MASH), have garnered unprecedented attention in recent years.^1,2 Although causality has not yet been unequivocally established, interventions targeting the gut microbiota, such as antibiotics and fecal microbiota transplantation, have been demonstrated to improve health.³ Although such interventions show unique clinical value in specific scenarios such as recurrent Clostridioides difficile infection,⁴ they typically show interindividual variability in efficacy and raise safety concerns, altogether underscoring the need for safer, more precise, and targeted strategies.⁵ A deeper understanding of the molecular mechanisms by which gut microbiota exert their functions in health and disease will be crucial to such goals.

Enzymes are intracellular proteins that perform defined biological processes, and enzyme-targeting drugs constitute a significant proportion of current therapeutics.⁶ In recent years, growing evidence has indicated that gut microbial enzymes are key mediators of microbiota-derived functions.⁷ Such enzymes contribute to CMDs pathogenesis primarily through 3 mechanisms: generating bioactive metabolites that influence intestinal barrier integrity, inflammation, and other essential physiological processes; regulating the homeostasis of critical host metabolites, such as ceramides and cholesterol; and metabolizing xenobiotics derived from diet and drugs, thereby modulating nutrient absorption and drug efficacy.

Given the complexity of the functions of gut microbiota, it is arguably overly simplistic to categorize them as symbionts that are probiotic or pathogenic. Rather, by identifying and characterizing key microbial enzymes, we will be able to precisely modulate gut microbiota functions in health and disease. When a clear enzymatic cause is identified, therapies targeting microbial enzymes capitalize on a function-driven mechanism. This allows for precision that is independent of taxonomy and avoids off-target consequences stemming from compositional heterogeneity of the functional microbes across individuals. The operational feasibility and druggability of these therapies are further supported by mature enzyme-based therapy development paradigms. Ultimately, enzyme-targeted interventions are expected to work alongside conventional whole-microbiota or strain-level approaches, thereby enriching the toolkit for developing gut microbiome-based therapeutics.

Approximately 25% to 40% of hospitalized adults are discharged to receive postacute care either at home through home health or in skilled nursing facilities, inpatient rehabilitation facilities, or long-term acute care hospitals.

This Narrative Review considers postacute care settings to assist hospital-based clinicians in effectively collaborating with patients, caregivers, and interdisciplinary care teams to facilitate transitions to high-quality postacute care.

Clinicians often care for patients who cannot return to their previous level of support in the community due to new functional impairments or complex posthospital care needs. After hospital discharge, these patients may require postacute care (PAC)—broadly defined as medical and rehabilitative services intended to help individuals recuperate and rehabilitate. PAC can be provided at home through home health (HH) or in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), and long-term acute care hospitals (LTACHs). A key criterion for PAC eligibility is the need for skilled nursing and/or rehabilitative services as determined by the treating physician.^1-3 Payers require that these health services be reasonable and necessary for the treatment of a specific illness or injury, and that given their complexity (eg, wound care, intravenous infusion), they be provided only by a health professional. Yet, clinicians often play a passive role in PAC planning; many report a lack of knowledge around PAC capabilities, quality, and constraints.^4-6

The epidemiology of PAC in the US is best understood for Traditional Medicare (or fee-for-service). Among hospitalized Medicare beneficiaries, approximately 40% were discharged to PAC in 2023: 18% to HH, 17% to SNF, 5% to IRFs, and 1% to LTACHs,⁷ accounting for approximately $60 billion of Medicare spending annually.⁷ Up to three-quarters of regional differences in Medicare spending are attributable to PAC, suggesting that discharge decisions are often driven by local practice norms rather than patient need. This underscores the need to improve and standardize PAC best practices.^8,9

Hospital-based physicians, nurse practitioners, and physician assistants play an important role in PAC discharge planning due to their in-depth understanding of a patient’s complex medical needs. A better understanding of the qualifications and services provided can help clinicians engage in a more helpful role in the PAC discharge planning process. This Narrative Review provides an overview of PAC settings with the goal of helping clinicians collaborate most effectively with patients, caregivers, and interdisciplinary care teams to promote transition to high-quality PAC. We present a general summary of the most common types of PAC, followed by a comparison of the supporting evidence for each PAC setting. Descriptions of elements of PAC are based on the benefits covered by Traditional Medicare, which generally inform other payers’ coverage policies. Lastly, we review best practices for clinicians to actively discuss PAC options with patients, helping to orchestrate transitions of care to PAC for eligible individuals.

Liver sinusoidal endothelial cells (LSECs) are specialised endothelial cells that orchestrate hepatic homeostasis within the liver sinusoid. Besides their key role in regulating intrahepatic vascular tone, trafficking and cellular crosstalk, their scavenging and immune-regulatory role makes them central to the development of liver disease. LSEC dysfunction includes loss of fenestrae, inflammatory activation and the gain of vasoconstrictive and prothrombotic functions. Robust evidence has demonstrated how preserving LSECs is crucial in a pathological context, placing LSECs at the centre of novel therapeutic and diagnostic strategies.

Ström et al. identify the rs115660502 variant in RAB3GAP2 associated with increased skeletal muscle capillary-to-fiber ratio and enriched in endurance athletes. This variant reduces RAB3GAP2 expression, enhancing endothelial proliferation, tube formation, and TNC secretion, thereby promoting exercise-like angiogenesis and microvascular remodeling in skeletal muscle.