The Effects of Prebiotic Supplementation with OMNi-LOGiC® FIBRE on Fecal Microbiome, Fecal Volatile Organic Compounds, and Gut Permeability in Murine Neuroblastoma-Induced Tumor-Associated Cachexia

Abstract

<jats:p>Malignant diseases can cause tumor-associated cachexia (TAC). Supplementation with prebiotic non-digestible carbohydrates exerts positive metabolic effects in experimental oncologic diseases. The aim of this project was to assess the effect of prebiotic supplementation with OMNi-LOGiC® FIBRE on intestinal microbiome, bacterial metabolism, gut permeability, and inflammation in a murine model of neuroblastoma (NB)-associated TAC. For this study, 2,000,000 NB cells (MHH-NB11) were implanted into athymic mice followed by daily supplementation with water or 200 mg prebiotic oligosaccharide (POS) OMNi-LOGiC® FIBRE (NB-Aqua, n = 12; NB-POS, n = 12). Three animals of each tumor group did not develop NB. The median time of tumor growth (first visibility to euthanasia) was 37 days (IQR 12.5 days) in the NB-Aqua group and 37 days (IQR 36.5 days) in the NB-POS group (p = 0.791). At euthanasia, fecal microbiome and volatile organic compounds (VOCs), gut permeability (fluorescein isothiocyanate-dextran (FITC-dextran), and gut barrier markers were measured. Values were compared to sham animals following injection of culture medium and gavage of either water or OMNi-LOGiC® FIBRE (SH-Aqua, n = 10; SH-POS, n = 10). Alpha diversity did not differ significantly between the groups. Principal coordinate analysis (PCoA) revealed clustering differences between Aqua and POS animals. Both NB and POS supplementation led to taxonomic alterations of the fecal microbiome. Of 49 VOCs, 22 showed significant differences between the groups. NB animals had significantly higher gut permeability than Aqua animals; POS did not ameliorate these changes. The pore and leak pathways of tight junctions did not differ between groups. In conclusion, our results suggest that NB-induced TAC causes increased gut permeability coupled with compositional changes in the fecal microbiome and VOC profile. Prebiotic supplementation with OMNi-LOGiC® FIBRE seemed to induce modifications of the fecal microbiome and VOC profile but did not improve gut permeability.</jats:p>

Cachexia, a Systemic Disease beyond Muscle Atrophy

“…Beside the tumor, another source of inflammation may come from the translocation of pathogen-associated molecular patterns (PAMPS) such as lipopolysaccharides (LPS) and peptidoglycans, arising from the gut microbiota. Gut barrier dysfunction has been described in several mouse models of cancer cachexia [ 105 , 106 , 107 ], with an alteration of the tight junctions, an increased gut permeability, morphological changes, a local immunosuppression, and a decreased expression in antimicrobial peptides. In the C26 model, this alteration in the gut barrier function was attributed to the increased systemic levels in IL-6 [ 108 ] and fostered by the emergence of specific opportunistic bacteria such as Klebsiella oxytoca [ 109 ].…”

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

“…After checking their reference lists, we excluded reviews, book chapters, case reports, conference articles, and study protocols, which resulted in 35 research articles being left. These articles were screened fully to assess their eligibility, and eight articles were accepted for inclusion based on exposure, study population, and outcome measures [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. After reviewing the reference lists of the included articles and broadening the term “disease” to (“heart failure” OR COPD OR “renal failure” OR HIV), one additional study was included in the review [ 21 ].…”

“…Moreover, additional research was performed to gain more insights into the relationship between gut permeability and muscle mass or function ( Figure 1 B). This study selection and data extraction was performed similarly to the first systematic search and resulted in the inclusion of eight studies [ 15 , 16 , 20 , 22 , 23 , 24 , 25 , 26 ].…”

“…POS supplementation did also not change Lactobacillus spp. abundance in these diseased mice [ 16 ]. Secondly, Bindels et al [ 17 ] also studied the effects of POS and, next to that, the effects of inulin in mice injected with BaF cells, inducing acute leukemia.…”

“…Therefore, a systematic search was performed to investigate the association between gut permeability and muscle mass or function. In total, eight studies were included, measuring both gut permeability and muscle mass or function in disease and aging models ( Table 2 ) [ 15 , 16 , 20 , 22 , 23 , 24 , 25 , 26 ]. All studies were performed in mice, except for the studies of Cuoco et al [ 22 ], Qi et al [ 25 ], and van der Meij et al [ 26 ], which concern human observational studies using matched controls to compare with patients and a young group to compare with elderly.…”