Aging is typically accompanied by biological and physiological changes that alter cellular functions. Two of the most predominant phenomena in aging include chronic low-grade inflammation (inflammaging) and changes in the gut microbiota composition (dysbiosis). Although a direct causal relationship has not been established, many studies have reported significant reductions in inflammation during aging through well-maintained gut health and microbial balance. Prebiotics and probiotics are known to support gut health and can be easily incorporated into the daily diet. Unfortunately, few studies specifically focus on their significance in reducing inflammation during aging. Therefore, this review summarizes the scientific evidence of the potential roles of probiotics and two types of prebiotics, resistant starch and resistant proteins, in later age. Studies have demonstrated that the oral consumption of bacteria that may contribute to anti-inflammatory response, such as Bifidobacterium spp., Akkermansia munichipilla, and Faecalis praunitzii, contributes significantly to the suppression of pro-inflammatory markers in elderly humans and aged animals. Colonic fermentation of resistant starch and proteins also demonstrates anti-inflammatory activity owing to the production of butyrate and an improvement in the gut microbiota composition. Collectively, probiotics, resistant starch, and resistant proteins have the potential to promote healthy aging.

Gut microbiota is an essential factor in the shaping of intestinal immune system development and driving inflammation in inflammatory bowel disease (IBD). We report the effects and microbe-host interactions underlying an intervention using fine powder of eggshell membrane (ESM) against IBD. ESM attenuated lipopolysaccharide-induced inflammatory cytokine production and promoted the Caco-2 cell proliferation by up-regulating growth factors in vitro. In a murine model of dextran sodium sulphate-induced colitis, ESM significantly suppressed the disease activity index and colon shortening. These effects were associated with significant ameliorations of gene expressions of inflammatory mediators, intestinal epithelial cell proliferation, restitution-related factors and antimicrobial peptides. Multifaceted integrated omics analyses revealed improved levels of energy metabolism-related genes, proteins and metabolites. Concomitantly, cecal metagenomic information established an essential role of ESM in improving dysbiosis characterized by increasing the diversity of bacteria and decreasing absolute numbers of pathogenic bacteria such as Enterobacteriaceae and E. coli, as well as in the regulation of the expansion of Th17 cells by suppressing the overgrowth of segmented filamentous bacteria. Such modulations have functional effects on the host; i.e., repairing the epithelium, regulating energy requirements and eventually alleviating mucosal inflammation. These findings are first insights into ESM’s modulation of microbiota and IBD suppression, providing new perspectives on the prevention/treatment of IBD.

Background: Cachexia is a life‐threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (Il10) gene transfer is known to improve cachexia by downregulating Il6. Here, we used an IL10‐knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre‐cachexia symptoms, which is particularly important for the development of cachexia therapeutics.Methods: Five‐week‐old male C57BL6/J mice were fed an AIN‐93G powdered diet (WT), and 5‐week‐old male B6.129P2‐Il10 < tm1Cgn>/J (IL10^−/−) mice were fed either the AIN‐93G diet (KO) or an 8% ESM‐containing diet (KOE) for 28 weeks. The tissue weight and levels of anaemia‐, blood glucose‐, lipid metabolism‐, and muscular and colonic inflammation‐related biochemical markers were measured. Transcriptomic analysis on liver and colon mucus and proteomic analysis on skeletal muscle were performed. Ingenuity Pathway Analysis was used to identify molecular pathways and networks. Caecal short‐chain fatty acids (SCFAs) were identified using HPLC, and caecal bacteria DNA were subjected to metagenomic analysis. Flow cytometry analysis was performed to measure the CD4⁺ IL17⁺ T cells in mesenteric lymph nodes.Results: The body weight, weight of gastrocnemius muscle and fat tissues, colon weight/length ratio, plasma HDL and NEFA, muscular PECAM‐1 levels (P < 0.01), plasma glucose and colonic mucosal myeloperoxidase activity (P < 0.05) and T helper (Th) 17 cell abundance (P = 0.071) were improved in KOE mice over KO mice. Proteomic analysis indicated the protective role of ESM in muscle weakness and maintenance of muscle formation (>1.5‐fold). Transcriptomic analysis revealed that ESM supplementation suppressed the LPS/IL1‐mediated inhibition of RXR function pathway in the liver and downregulated the colonic mucosal expression of chemokines and Th cell differentiation‐related markers (P < 0.01) by suppressing the upstream BATF pathway. Analysis of the intestinal microenvironment revealed that ESM supplementation ameliorated the microbial alpha diversity and the abundance of microbiota associated with the degree of inflammation (P < 0.05) and increased the level of total organic acids, particularly of SCFAs such as butyrate (2.3‐fold), which could inhibit Th1 and Th17 production.Conclusions: ESM supplementation ameliorated the chief symptoms of cachexia, including anorexia, lean fat tissue mass, skeletal muscle wasting and reduced physical function. ESM also improved colon and skeletal muscle inflammation, lipid metabolism and microbial dysbiosis. These results along with the suppressed differentiation of Th cells could be associated with the beneficial intestinal microenvironment and, subsequently, attenuation of pre‐cachexia. Our findings provide insights into the potential of ESM in complementary interventions for pre‐cachexia prevention.

Diet-induced obesity is often associated with gut microbiota dysbiosis, lipid metabolism disorders, and chronic inflammation. Consumption of the pseudocereal Amaranthus mangostanus has multiple nutritional benefits. We investigated the effects of dietary amaranth on lipid metabolism and gut microbiota in high-fat (HF) diet-fed mice. C57BL/6J mice were provided either a control diet, HF diet, or HF diet containing 10% amaranth powder (Ama) for 8 weeks. Ama supplementation significantly reduced the levels of triglycerides, total cholesterol, and phospholipids in the liver. Moreover, Ama supplementation downregulated the expression of lipogenesis-related genes including Hmgcr, Fdt1, and Sgle in the liver. The gut microbiota analysis showed that Ama supplementation reversed HF diet-induced reduction in bacterial diversity and richness. Additionally, beta diversity analysis of the inter-group variability in community structure showed a clear separation between the HF and Ama groups. Linear discriminant analysis effect size analysis revealed that 11 taxa were enriched in the Ama group, whereas 9 taxa were increased in the HF group. We found that family Porphyromonadaceae and unclassified S24-7 showed a strong positive and negative correlation with the lipid parameters, respectively. Taken together, these results indicated that dietary Ama may attenuate HF diet-induced deterioration of gut microbiota structure and hepatic lipid metabolism.

Skin aging is one of the hallmarks of the aging process that causes physiological and morphological changes. Recently, several nutritional studies were conducted to delay or suppress the aging process. This study investigated whether nutritional supplementation of the eggshell membrane (ESM) has a beneficial effect on maintaining skin health and improving the skin aging process in vitro using neonatal normal human epidermal keratinocytes (NHEK-Neo) and in vivo using interleukin-10 knockout (IL-10 KO) mice. In NHEK-Neo cells, 1 mg/mL of enzymatically hydrolyzed ESM (eESM) upregulated the expression of keratinocyte differentiation markers, including keratin 1, filaggrin and involucrin, and changed the keratinocyte morphology. In IL-10 KO mice, oral supplementation of 8% powdered-ESM (pESM) upregulated the expression of growth factors, including transforming growth factor β1, platelet-derived growth factor-β and connective tissue growth factor, and suppressed skin thinning. Furthermore, voltage-gated calcium channel, transient receptor potential cation channel subfamily V members were upregulated by eESM treatment in NHEK-Neo cells and pESM supplementation in IL-10 KO mice. Collectively, these data suggest that ESM has an important role in improving skin health and aging, possibly via upregulating calcium signaling.

Prevention of muscle atrophy contributes to improved quality of life and life expectancy. In this study, we investigated the effects of laurel, selected from 34 spices and herbs, on dexamethasone (DEX)-induced skeletal muscle atrophy and deciphered the underlying mechanisms. Co-treatment of C2C12 myotubes with laurel for 12 h inhibited the DEX-induced expression of intracellular ubiquitin ligases—muscle atrophy F-box (atrogin-1/MAFbx) and muscle RING finger 1 (MuRF1)—and reduction in myotube diameter. Male Wistar rats were supplemented with 2% laurel for 17 days, with DEX-induced skeletal muscle atrophy occurring in the last 3 days. Laurel supplementation inhibited the mRNA expression of MuRF1, regulated DNA damage and development 1 (Redd1), and forkhead box class O 1 (Foxo1) in the muscles of rats. Mechanistically, we evaluated the effects of laurel on the cellular proteolysis machinery—namely, the ubiquitin/proteasome system and autophagy—and the mTOR signaling pathway, which regulates protein synthesis. These data indicated that the amelioration of DEX-induced skeletal muscle atrophy induced by laurel, is mainly mediated by the transcriptional inhibition of downstream factors of the ubiquitin-proteasome system. Thus, laurel may be a potential food ingredient that prevents muscle atrophy.