Alpha-gal syndrome (AGS), an emerging tick-borne carbohydrate hypersensitivity, has gained increasing recognition for its atypical presentation and delayed food-related allergic reactions. While urticaria and anaphylaxis dominate the clinical narrative, gastrointestinal (GI) manifestations-including abdominal pain, diarrhea, bloating, and cramping-are common and often underrecognized. These nonspecific GI symptoms create significant diagnostic overlap with prevalent functional and food-related disorders such as non-celiac gluten sensitivity (NCGS) and lactose intolerance. Consequently, many patients with AGS undergo unnecessary dietary restrictions, prolonged symptom burden, or misdirected therapies before an accurate diagnosis is established. The knowledge gap lies in the limited awareness of AGS as a differential diagnosis for food-related GI complaints, especially in regions endemic to tick exposure. Unlike gluten or lactose intolerance, AGS reactions are characterized by a unique delayed onset (2-6 hours postprandially) and a distinct immunologic mechanism mediated by IgE to galactose-α-1,3-galactose. However, clinicians rarely consider AGS when evaluating chronic, unexplained food-triggered symptoms, perpetuating diagnostic blind spots. Current guidelines for evaluating NCGS and lactose intolerance seldom incorporate testing for alpha-gal IgE, despite growing evidence that a subset of misdiagnosed patients may in fact harbor AGS. Clinically, this misclassification carries significant consequences: Patients may continue mammalian food exposure with risk of escalating allergic reactions, including life-threatening anaphylaxis, while adhering to unnecessary or ineffective gluten-free or lactose-free diets. Raising awareness, integrating alpha-gal IgE testing into gastroenterology workups, and refining diagnostic algorithms are urgently needed. Addressing this blind spot has the potential to reduce morbidity, improve diagnostic accuracy, and optimize individualized patient care.
Ramkumar D, Marty A, Ramkumar J, Rosencranz H, Vedantham R, et al.
One health (Amsterdam, Netherlands) •
Non-communicable diseases (NCDs) pose a global health challenge, leading to substantial morbidity, mortality, and economic strain. Our review underscores the escalating incidence of NCDs worldwide and highlights the potential of regenerative agriculture (RA) products in mitigating these diseases. We also explore the efficacy of dietary interventions in NCD management and prevention, emphasizing the superiority of plant-based diets over those high in processed foods and red meat. Examining the role of the gut microbiome in various diseases, including liver disorders, allergies, metabolic syndrome, inflammatory bowel disease, and colon cancer, we find compelling evidence implicating its influence on disease development. Notably, dietary modifications can positively affect the gut microbiome, fostering a symbiotic relationship with the host and making this a critical strategy in disease prevention and treatment. Investigating agricultural practices, we identify parallels between soil/plant and human microbiome studies, suggesting a crucial link between soil health, plant- and animal-derived food quality, and human well-being. Conventional/Industrial agriculture (IA) practices, characterized in part by use of chemical inputs, have adverse effects on soil microbiome diversity, food quality, and ecosystems. In contrast, RA prioritizes soil health through natural processes, and includes avoiding synthetic inputs, crop rotation, and integrating livestock. Emerging evidence suggests that food from RA systems surpasses IA-produced food in quality and nutritional value. Recognizing the interconnection between human, plant, and soil microbiomes, promoting RA-produced foods emerges as a strategy to improve human health and environmental sustainability. By mitigating climate change impacts through carbon sequestration and water cycling, RA offers dual benefits for human and planetary health and well-being. Emphasizing the pivotal role of diet and agricultural practices in combating NCDs and addressing environmental concerns, the adoption of regional RA systems becomes imperative. Increasing RA integration into local food systems can enhance food quality, availability, and affordability while safeguarding human health and the planet's future.
Boyce RM, Schulz A, Mansour O, Giandomenico D, Farel CE, et al.
Open forum infectious diseases •
Alpha-gal syndrome (AGS) is a recently described allergy to galactose-α-1,3-galactose, an oligosaccharide present in mammalian meat. AGS can present with angioedema, urticaria, and anaphylaxis arising 3-6 hours after ingestion, although symptoms such as gastrointestinal distress, fatigue, and arthralgias are also reported. Because AGS appears to be associated with tick bites, patients may present to infectious diseases (ID) clinics for evaluation. We documented a series of 5 patients referred to the University of North Carolina ID Clinic between 2020 and 2022 for various tick-borne infections that were found to have symptoms and laboratory testing consistent with AGS. Patients were subsequently referred to the Allergy and Immunology Clinic. Patients were referred to the ID Clinic for persistent symptoms following positive tick-borne disease testing or presumed tick-borne infection. All patients had an elevated alpha-gal immunoglobulin E and clinical presentation consistent with AGS. Common symptoms included episodic gastrointestinal distress (eg, cramping, nausea, diarrhea), fatigue, arthralgias, and subjective cognitive impairment, but a notable absence of severe anaphylaxis. Four patients were seen by at least 1 nonallergy specialist prior to referral to ID. Patients reported substantial improvement in their symptoms following dietary restriction. ID physicians should be aware of AGS as a cause of persistent, nonspecific symptoms following a tick exposure or tick-borne illness. Further research is needed to determine the prevalence of alpha-gal sensitization and AGS following tick-borne bites.
Carson DA, Kopsco H, Gronemeyer P, Mateus-Pinilla N, Smith GS, et al.
One health (Amsterdam, Netherlands) •
The rising incidence of tick-borne disease (TBD) underscores the importance of proficiency in TBD diagnosis. Clinicians' knowledge about vector ticks and TBDs in their area may influence whether patients are questioned about potential tick exposure and the consideration of diagnostic testing for TBDs. Our objective was to assess the knowledge, attitudes, and practices of Illinois clinicians towards ticks and TBDs. The study aimed to 1) identify predictors associated with knowledge, 2) identify knowledge gaps, and 3) evaluate attitudes and practices related to TBDs. A web-based knowledge, attitudes, and practices survey about Illinois ticks and TBDs was disseminated to physicians, mid-level practitioners, and nurses between August 2020 and February 2022. Poisson regression analysis was conducted to identify predictors of higher scores. Of 346 respondents, 80% correctly identified Lyme disease as endemic to Illinois, and 95% were familiar with diagnostic testing for Lyme. Knowledge of other TBDs present in the state was highest among physicians, yet only 26% of physicians believed Rocky Mountain spotted fever (RMSF) to be present in Illinois, and only 17% believed ehrlichiosis to be endemic. Only 32% of physicians knew the cause of Alpha-gal syndrome and fewer than 18% were aware of available diagnostic testing. Tick or TBD-related education within the past two years was the most significant predictor of higher scores, increasing overall knowledge scores by 26% (RR 1.26, 95% CI 1.13-1.41) and increasing scores specific to TBDs by 42% (RR 1.42, 95% CI 1.19-1.69). Illinois clinicians were informed about Lyme disease but lacked knowledge of other TBDs endemic to the state, including RMSF, ehrlichiosis, and Alpha-gal syndrome. The strongest predictor of knowledge was tick/TBD training in the previous two years, highlighting the importance of frequent region-specific training on ticks and TBDs.
