Muscle wasting is a frequently observed, inflammation-driven condition in aging and disease, known as sarcopenia and cachexia. Current treatment strategies target the muscle directly and are often not able to reverse the process. Because a reduced gut function is related to systemic inflammation, this might be an indirect target to ameliorate muscle wasting, by administering pro-, pre-, and synbiotics. Therefore, this review aimed to study the potential of pro-, pre-, and synbiotics to treat muscle wasting and to elucidate which metabolites and mechanisms affect the organ crosstalk in cachexia. Overall, the literature shows that Lactobacillus species pluralis (spp.) and possibly other genera, such as Bifidobacterium, can ameliorate muscle wasting in mouse models. The beneficial effects of Lactobacillus spp. supplementation may be attributed to its potential to improve microbiome balance and to its reported capacity to reduce gut permeability. A subsequent literature search revealed that the reduction of a high gut permeability coincided with improved muscle mass or strength, which shows an association between gut permeability and muscle mass. A possible working mechanism is proposed, involving lactate, butyrate, and reduced inflammation in gut–brain–muscle crosstalk. Thus, reducing gut permeability via Lactobacillus spp. supplementation could be a potential treatment strategy for muscle wasting.

Advanced Glycation End products (AGEs) are a heterogeneous group of stable reaction products formed when amino acids, peptides, or proteins are glycated by the non-enzymatic Maillard Reaction. The formation and accumulation of these products in vivo are linked to many inflammation-based pathological outcomes and part of the pathophysiology of non-communicable diseases like eye cataracts and Alzheimer's disease. Since our diet contains high levels of the same compounds, it has been questioned whether their consumption is also detrimental to health. However, this is still under debate. In this context, the intestinal epithelium is an important target tissue since it is chronically exposed to relatively high concentrations of dietary AGEs. This review summarizes the current evidence on the impact of dietary AGEs on the intestinal epithelium and critically reflects on its methodology. In healthy rodent models, an inflammation-independent impaired intestinal barrier function is claimed; however, dietary AGEs showed anti-inflammatory activity in IBD models. In vitro studies could be a valuable tool to unravel the underlying mechanisms of these effects, however the available studies face some limitations, e.g. lack of the physicochemical characterization of the glycated proteins, the inclusion of the proper controls and the dose-dependency of the effect. In addition, studies using more advanced in vitro models like intestinal organoids and co-cultures with immune cells exposed to gut microbial metabolites derived from the fermentation of AGEs are still needed.

Advanced Glycation End products (AGEs) are covalent protein adducts formed through the Maillard reaction. High dietary intake might harm human health, however studies on their impact remain inconclusive. A proposed mechanism is that dietary AGEs trigger inflammation by interacting with the AGEs receptor (RAGE). However, in vitro studies on dietary AGE-RAGE signaling have reported inconsistent results, probably due to methodological issues. This study aimed to seek a standardized model of dietary AGE-RAGE signaling. In vitro models were characterized for surface and total RAGE expression using flow cytometry. Both commercially available and in-house prepared dietary AGE preparations were analyzed for AGE levels, aggregation, and LPS content, then tested in the model with the highest surface RAGE expression. All immortalized cell lines expressed intracellular RAGE, while its surface expression was marginal or even absent. Only M-CSF-differentiated M0 macrophages showed significant surface RAGE expression. Some glycated dietary proteins induced inflammation in this model, but not all. While these proteins showed RAGE affinity in a chemical assay, the inflammatory response could not be reduced by the RAGE antagonist FPS-ZM1. Interestingly, co-incubation with the LPS scavenger PMB reduced inflammation despite negligible LPS levels in the sample. These results challenge the hypothesis that dietary AGEs cause inflammation via RAGE activation, as glycated dietary proteins alone do not seem to induce acute inflammation. To better understand the biological activity of dietary AGEs, future studies should confirm surface RAGE expression, detail glycation methods and glycated protein characteristics, and account for LPS interference.