Featured Articles

Maternal immune modulations are critical for fetal development. Without tolerance of fetal markers there is a risk of complications, such as preterm birth and miscarriage. It is known that the gut microbiome helps shape the immune system in healthy individuals and that dysbiosis can drive inflammation and potentially autoimmune diseases. However, in the context of pregnancy the role that the microbiome plays in maternal-fetal tolerance is unclear. A recent publication by Dr. Melody Zeng’s group focused on how the maternal microbiome regulates maternal-fetal tolerance. In this study, they demonstrate that pregnancy alters the microbiome significantly. Bacterial diversity is reduced and there... read more

Glioblastoma remains one of the most aggressive and treatment-resistant brain tumors, largely due to a profoundly immunosuppressive tumor microenvironment that limits the efficacy of current therapies. Increasing evidence highlights the importance of tryptophan metabolism, particularly the kynurenine pathway, in shaping immune responses in cancer and neuroinflammatory conditions. Despite extensive interest in kynurenine pathway metabolites, the specific role of kynurenic acid (KYNA) in glioblastoma remains unclear. Understanding how KYNA influences the cellular ecosystem of the tumor could reveal new strategies to overcome immune resistance. In this study, Chen et al. generate a comprehensive single-cell transcriptomic atlas of the glioblastoma microenvironment to uncover... read more

Infants born to women living with HIV (WLWH) who remain uninfected themselves still face markedly higher risks of infection, impaired growth, and neurodevelopmental challenges. Although chronic immune activation is a well-established feature of maternal HIV, how this biology affects the infant remains to be fully understood. A new longitudinal metabolomics study by Tobin and colleagues brings tryptophan metabolism to the center of this discussion. Profiling 1,426 breast-milk samples from 326 Zambian mothers across 18 months postpartum, the authors uncovered a striking and persistent signature. Milk from WLWH contains significantly less tryptophan and more kynurenine at every stage of lactation. These alterations... read more

Multiple sclerosis (MS) is an autoimmune disorder that targets oligodendrocytes, leading to neuroinflammation, demyelination, and neurodegeneration. Chronic inflammation is known to activate the kynurenine pathway (KP), which can generate the neurotoxic metabolites quinolinic acid (QA) and 3-hydroxykynurenine. Many studies have focused on QA and kynurenic acid (KA), as the QA/KA ratio provides an indication of whether the microenvironment is predominantly neurotoxic or neuroprotective. In a recent study, Prof. Zimmer and colleagues used targeted metabolomics to investigate alterations in the KP metabolite profile in patients with MS. Individuals with MS showed a lower kynurenine/tryptophan (K/T) ratio, suggesting activation of the KP. The... read more

Circadian disruption is an emerging global health challenge. Shift work workers exposed to irregular light–dark schedules are susceptible to increase risk for sleep disturbance and cognitive decline. Similarly, long-COVID research has shown that nearly half of affected individuals report persistent sleep disturbances a year post-infection, often accompanied by fatigue, memory impairment, and brain fog. Together, these examples highlight a growing recognition: disrupted sleep and circadian misalignment are tightly linked to impaired cognition with implications for upregulation of the kynurenine pathway (see 2024 April/May highlight) and serotonin depletion (see 2023 Oct highlight). A new study by Jing Liao and colleagues (2025) provides... read more

Tryptophan metabolism has long been recognised as a biochemical intersection where diet, metabolism, and brain function converge. Central to serotonin biosynthesis is tryptophan hydroxylase (TPH), the rate-limiting enzyme that converts dietary tryptophan into serotonin (5-HT). For decades, TPH1 was viewed as the “peripheral” isoform and TPH2 as the “brain” isoform. However, two recent studies are reframing this view, showing that TPH2 is not confined to the brain but also functions in peripheral systems, including adipose tissue, where it emerges as a driver of obesity-linked metabolic dysfunction and as a molecular player in the neurobiology of autism. In the central nervous... read more

Gray mold, Botrytis cinerea, infects over 200 plant species and has significant impact on the agriculture industry, yearly >$10 billion of crop lost worldwide due to this pathogenic fungus. Currently the treatment for B. cinerea is spraying plants with fungicide and the annual cost of is estimated to be >$1 billion globally (DeLong et al., 2020) adding to the economic burden. Unfortunately, due to its rapid lifecycle and overuse of fungicides, this pathogenic fungus has a high tendency of developing fungicide resistance therefore, multiple fungicide classes are often combined to treat crops thereby creating a vicious circle. Fungicide exposure (inhalation... read more

COVID‑19 induces profound shifts in host metabolism and immune regulation. Most notably, depletion of NAD⁺ and dysregulation of tryptophan metabolism via the KP. NAD⁺ is essential for cellular energy, DNA repair, and innate antiviral responses, but during SARS‑CoV‑2 infection, NAD⁺ levels drop due to increased PARP activity and inflammation-associated oxidative stress. At the same time, pro‑inflammatory cytokines (e.g., IFN‑γ, IL‑6) activate indoleamine 2,3‑dioxygenase (IDO), diverting tryptophan into the KP. This shift leads to both reduced serotonin synthesis and accumulation of immunomodulatory metabolites like kynurenine and quinolinic acid — a hallmark seen in COVID‑19 and associated with worse outcomes and cognitive... read more

Elevated levels of metals, including manganese (Mn), iron, and copper, have been associated with motor disease. These metals have been shown to accumulate in the basal ganglia and buildup is associated with motor deficits. However, chelating therapeutics are not as effective, suggesting that metal toxicity might induce microenvironmental changes contributing to motor deficits. It is well known that kynurenine pathway (KP) metabolites can play a role in inflammation (quinolinic acid (QUIN), and 3-hydroxykynurenine (3-HK)), oxidative stress (QUIN), and neurotoxicity (QUIN, 3-HK, and 3-HAA) which may lead to degeneration and play a role in neuromuscular decline (see 2023 April Highlight). Alternatively, upregulation... read more

Neurodevelopmental disorders, including autism spectrum disorders, have been increasingly associated with prenatal environmental factors. One emerging contributor is maternal immune activation (MIA) which is often triggered by infection or metabolic stress during pregnancy. Building on previous findings showing the importance of tryptophan (TRP) metabolism during pregnancy (See 2023 August highlight), this new preclinical study explores how a high-fat maternal diet (HFD) can initiate MIA, disrupt TRP metabolism and lead to behavioral deficits in male offspring. In this study, Sun et al., show that HFD during pregnancy activates immune pathways involving TLR4 and IL-17a, leading to increased placental and fetal expression... read more

The kynurenine pathway (KP) is well known for its essential roles in various physiological processes, from immune tolerance to regulating glucose metabolism in astrocytes (See 2024 August highlight).  While we have a general understanding of how the metabolites function in this pathway, the specific roles and chemical fates of each metabolite are still being uncovered. Recent discoveries, like the newly identified role of anthranilic acid in controlling feeding behavior (See 2024 November highlight), show there’s still much to learn. Among the many metabolites, the first one, N-formylkynurenine (NFK), has historically been overlooked and simply seen as a transient precursor to... read more

Low levels of kynurenic acid (KYNA) has been linked to mood disorders, including depression, and likely contributes to the pathophysiology of the disorder. In fact, it has been suggested that this neuroprotective metabolite could be used as a biomarker for the diagnosis of depression and treatment response (Erabi et al., 2020). Kynurenine aminotransferase (KAT) activity is likely the root cause of decreased KYNA in depression. Animal models of depression are key in identifying potential therapeutics and understanding the underlying pathophysiology of depression. In a recent study, Dr. Masaru Tanaka and colleagues developed a knockout mouse model to investigate the effects... read more