Immunity from your plate — can fasting strengthen the body more than supplements?

Aim of the study: Chronic low-grade inflammation has been associated with insulin resistance, diabetes, atherosclerosis, obesity, and metabolic syndrome (MetS). A proinflammatory environment contributes to several metabolic disturbances and possibly the development of MetS. Dietary approaches have defined impact on immune function and putative antiinflammatory effects.

Results: Thirteen randomized controlled trials with a total of 2017 patients were included. Low-fat diets (29 ± 2% energy from fats) decreased C-reactive protein compared with control diets (SMD: -0.98; 95% CI: -1.6 to -0.35; P = 0.002). Low-carbohydrate diets (23 ± 10% energy from carbohydrates; SMD: -0.33; 95% CI: -0.63 to -0.03; P = 0.004) and multimodal interventions (SMD: -1.02; 95% CI: -1.97 to -0.07; P = 0.04) were able to induce significant weight loss. Low-carbohydrate diets were able to decrease insulin (SMD: -0.33; 95% CI: -0.63 to -0.03; P = 0.03). C-reactive protein; however, this effect is also dependent on weight loss. Furthermore, low-carbohydrate diets have beneficial effects on insulin and body weight. Dietary approaches should mainly be tried to reduce macronutrients and enrich functional food components such as vitamins, flavonoids, and unsaturated fatty acids. People with MetS will benefit most by combining weight loss and anti-inflammatory nutrients.

Aim of the study: Aging is accompanied by a progressive decline in immune function, known as immunosenescence, and by a chronic low-grade inflammatory state, termed inflammaging. Both conditions contribute to increased susceptibility to infections, reduced vaccine responses, and the development of age-related diseases.

Results: By reducing oxidative stress and inflammaging, IF may mitigate frailty in older adults or delay its progression when initiated earlier. By integrating insights from immunometabolism and gerontology, this review highlights the potential role of IF as a non-pharmacological strategy to promote healthy immune aging and support functional outcomes in older adults. However, evidence in frail older adults remains limited, and randomized trials in this population are warranted. Future research should directly compare IF with isocaloric non-fasting regimens, include long-term follow-up, and carefully characterize safety and adherence in high-risk groups before IF can be routinely recommended for immune aging.

Aim of the study: Although intrinsic metabolic pathways have critical roles in T cell function1,2, systemic nutrient availability is in constant flux. Yet, how postprandial metabolism affects T cell fate has been less studied.

Results: Human or murine T cells from fed hosts had higher metabolic capacity than those from fasted hosts, and this increase in capacity persisted after activation and expansion in vitro or in vivo. Triglyceride-rich chylomicrons in serum were drivers of postprandial immunometabolic reprogramming, and chylomicrons primed mTORC1-dependent translation ex vivo and after activation, which markedly enhanced effector function after priming. Human postprandial CAR-T cells manufactured from the same donor showed a therapeutic advantage over T cells collected while individuals were fasted. Thus, postprandial metabolism imparts durable metabolic and functional advantages to T cells, highlighting the importance of considering nutritional status in immunological analysis, vaccination and generation of cellular therapies.

Aim of the study: Old age is characterized by a peculiar low-grade, chronic, and "sterile" inflammatory state, which has been termed "inflammaging." This is believed to substantially contribute to the pathogenesis of many age-related diseases and to the progression of the ageing process. An adequate nutritional status is of great importance for maintaining proper immune system functionality and preventing frailty in the elderly.

Results: Dietary components may affect inflammation directly, counteracting the low grade age-related inflammation. In this regard, healthy diets, including the Mediterranean diet, are associated with lower concentrations of inflammatory mediators, like C-reactive protein (CRP) and Tumor Necrosis Factor-α (TNF-α), that are hallmarks of inflammaging. Among the components of a healthy diet, a higher intake of whole grains, vegetables and fruits, nuts and fish are all associated with lower inflammation. One area of promising research is the microbiome-ageing interaction. Indeed, dysbiosis plays a role in sub-optimal metabolism, immune function and brain function and contributes to the poor health and impaired well-being associated with ageing. Modulation of the gut microbiota has shown promising results in some disorders.

Aim of the study: To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020.

Results: What is Known: • Gut microbiota-modulating interventions are biologically plausible adjunctive strategies in paediatric type 1 diabetes. • Earlier paediatric reviews included few randomised trials and reported inconsistent glycaemic findings. What is New: • This updated review included 12 randomised controlled trials involving 808 children and adolescents. • It adds a structured synthesis of immune-inflammatory, microbiota/barrier, metabolite-related and safety outcomes beyond glycaemic endpoints.

Aim of the study: Surgical injury compresses tissue damage, neuroendocrine stress, pain, fasting, microbial exposure, and repair into a brief interval of intense immune activity. Although anesthetic, analgesic, and nutritional care are usually examined separately, each can affect cytokine release, immune-cell trafficking, oxidative stress, macrophage activity, gut barrier integrity, substrate availability, and inflammatory resolution.

Results: Current evidence indicates that anesthetic and analgesic strategies can alter inflammatory or immune-cell phenotypes, and these changes are most informative when interpreted as surrogate or mechanistic endpoints linked to patient-important outcomes. Immunonutrition has the clearest clinical evidence in gastrointestinal cancer surgery, particularly among nutritionally vulnerable or high-risk patients, although effects vary with formula composition, timing, route, adherence, procedure, and comparator. Direct trials of integrated anesthesia-analgesia-immunonutrition pathways are now needed to connect these mechanistic pathways with recovery outcomes. Risk-stratified studies can use this framework to examine both component-specific effects and interactions across the wider pathway.

Aim of the study: Okra pods (Abelmoschus esculentus (L.) Moench) are known as a vegetable, the mucilage of which possesses many bioactivities. Okra mucilage (OM) is a carbohydrate-rich natural extract containing polysaccharides and other bioactive components.

Results: Notably, the regulatory effects of OM were comparable to mesalazine. In fasting-induced intestinal injury, OM restored microbial balance by regulating taxa such as Enterobacteriaceae and Erysipelotrichaceae, and downregulated gluconeogenesis-related genes including Klf15, Pck1, and Hmgcs2. OM upregulated genes involved in epithelial barrier function and immune homeostasis such as Btnl7, Btnl8, regulating pathways HIF-1, PI3K-Akt, MAPK and glycolysis/gluconeogenesis pathways. These findings demonstrate that OM alleviates intestinal injury by modulating gut microbiota, suppressing inflammation, and restoring intestinal immune and metabolic homeostasis, highlighting its potential as a natural mucilage-derived ingredient for maintaining intestinal homeostasis.

Aim of the study: Prolonged preoperative fasting is associated with intestinal dysbiosis, impaired mucosal homeostasis, and delayed postoperative recovery. Combined nutritional supplementation with glutamine, dietary fiber, and oligosaccharides has the potential to protect intestinal function during nutritional stress. In this study, we investigated the effects of this nutritional combination in a rat model of prolonged fasting.

Results: Fasting significantly reduced body weight, jejunal villous height, cecal weight, and the concentrations of acetate, n-butyrate, and n-valerate. Fasting was also associated with exploratory changes in gut microbiota composition and increased the expression of several Toll-like receptor (TLR), barrier, and autophagy-related genes in the jejunum. Supplementation with glutamine, dietary fiber, and oligosaccharides significantly attenuated the fasting-induced reduction in cecal weight and suppressed the upregulation of TLR5, TLR6, TLR8, CLDN1, CLDN3, OCLN, ZO-1, MUC3, ATG5, ATG12, Beclin1, p62, and LC3. Microbiota analysis showed that the relative abundance of sequences tentatively assigned to Lactobacillus reuteri in the supplemented group was comparable to that in the control group, whereas sequences tentatively assigned to Bifidobacterium animalis were detected predominantly in the supplemented group.