The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting, a Systematic Review-Gut Permeability as Potential Treatment Target.

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.

Immunomodulating effects of 13- and 16-hydroxylated docosahexaenoyl ethanolamide in LPS stimulated RAW264.7 macrophages.

Docosahexaenoyl ethanolamide (DHEA), the ethanolamine conjugate of the n-3 long chain polyunsaturated fatty acid docosahexaenoic acid, is endogenously present in the human circulation and in tissues. Its immunomodulating properties have been (partly) attributed to an interaction with the cyclooxygenase-2 (COX-2) enzyme. Recently, we discovered that COX-2 converts DHEA into two oxygenated metabolites, 13- and 16-hydroxylated-DHEA (13- and 16-HDHEA, respectively). It remained unclear whether these oxygenated metabolites also display immunomodulating properties like their parent DHEA. In the current study we investigated the immunomodulating properties of 13- and 16-HDHEA in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The compounds reduced production of tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß and IL-1Ra, but did not affect nitric oxide (NO) and IL-6 release. Transcriptome analysis showed that the compounds inhibited the LPS-mediated induction of pro-inflammatory genes (InhbA, Ifit1) and suggested potential inhibition of regulators such as toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 3 (IRF3), whereas anti-inflammatory genes (SerpinB2) and potential regulators IL-10, sirtuin 1 (Sirt-1), fluticasone propionate were induced. Additionally, transcriptome analysis of 13-HDHEA suggests a potential anti-angiogenic role. In contrast to the known oxylipin-lowering effects of DHEA, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses revealed that 13- and 16-HDHEA did not affect oxylipin formation. Overall, the anti-inflammatory effects of 13-HDHEA and 16-HDHEA are less pronounced compared to their parent molecule DHEA. Therefore, we propose that COX-2 metabolism of DHEA acts as a regulatory mechanism to limit the anti-inflammatory properties of DHEA.