Background Recent data suggested a role of gut microbiota and antibiotic use on immune checkpoint inhibitors efficacy. We aimed to evaluate the impact of early use of antibiotic (EUA), blood microbiome and plasmatic citrulline (marker of the intestinal barrier) on nivolumab efficacy in non-small cell lung cancer (NSCLC). Methods We included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between 2014 and 2017. Blood microbiome was analyzed at month (M) M0 and M2. Citrulline rates were evaluated at M0, M2, M4 and M6. Results Seventy-two patients were included (EUA in 42%). Overall survival (OS) was longer without EUA (median 13.4 months) than with EUA (5.1 months, p = 0.03). Thirty-five patients (49%) had plasma samples available. High citrulline rate (≥20 μM) at M0 was associated with tumor response (p = 0.084) and clinical benefit (nivolumab > 6 months) (p = 0.002). Median progression-free survival (PFS) was 7.9 months (high citrulline) vs 1.6 months (low citrulline) (p < 0.0001), and median OS were respectively non reached vs 2.2 months (p < 0.0001). Patients with EUA had lower median citrulline rates at M0: 21 μM (IQR 15.0–30.8) vs 32 μM (IQR 24.0–42.0) without EUA (p = 0.044). The presence of specific bacterial DNA in blood at M0 was associated with response and clinical benefit (Peptostreptococcae, Paludibaculum, Lewinella) or with tumor progression (Gemmatimonadaceae). Multivariate analyses on PFS and OS confirmed the prognostic role of citrulline and blood microbiome. Conclusions EUA is associated with shorter OS with nivolumab and lower citrulline rates. Plasma citrulline and blood microbiome appear to be promising predictive factors of nivolumab efficacy.

As older adults tend to reduce their intake of animal-source proteins, plant-source proteins may offer valuable resources for better protein intake. The aim of this study was to assess whether the pea proteins can be used to achieve blood amino acid levels that stimulate muscle protein synthesis. We measured variations in plasma amino acid concentrations in young and older adults given pea (NUTRALYS^® S85 Plus) or whey proteins either alone or in a standardized meal. The effect of amino acid concentrations on protein synthesis in C2C12 myotubes was determined. In terms of results, plasma amino acid concentrations reflected the difference between the amino acid contents of whey and pea proteins. Blood leucine showed a greater increase of 91 to 130% with whey protein compared to pea protein, while the opposite was observed for arginine (A greater increase of 147 to 210% with pea compared to whey). Culture media prepared with plasmas from the human study induced age-dependent but not protein-type-dependent changes in myotube protein synthesis. In conclusion, pea and whey proteins have the same qualities in terms of their properties to maintain muscle protein synthesis. Pea proteins can be recommended for older people who do not consume enough animal-source proteins.

N-carbamoyl putrescine (NCP), the decarboxylation derivative of citrulline, metabolically related to polyamines, may exert biological effects in mammals. The aim of this study was (i) to evaluate the nutritional properties of NCP in healthy rats and (ii) to determine the effect of NCP administration on muscle metabolism in malnourished old rats. The nutritional properties of NCP were first evaluated in 20 8-week-old male rats randomized to receive for two weeks a standard diet either alone (C group) or supplemented with NCP, 5 or 50 mg/kg/d. In a second study, 29 malnourished 18-month-old male rats were studied either before or after a 4-day refeeding with a standard diet either alone (REN group) or supplemented with NCP, 1 or 10 mg/kg/d. NCP had no effect on weight gain and body composition in either of the two studies. In healthy rats, muscle protein content was significantly increased in the soleus with NCP 5 mg/kg/d. A decrease in plasma glutamine and kidney spermine was observed at the 50 mg/kg/d dose; otherwise, no significant changes in plasma chemistry and tissue polyamines were observed. In malnutrition-induced sarcopenic old rats, refeeding with NCP 10 mg/kg/d was associated with higher tibialis weight and a trend for increased protein content in extensor digitorum longus (EDL). While the muscle protein synthesis rate was similar between groups, ribosomal protein S6 kinase was increased in tibialis and higher in the EDL in NCP-treated rats. The muscle RING-finger protein-1 expression was decreased in tibialis and urinary 3-methyl-histidine to creatinine ratio slightly lower with the supply of NCP. However, this initial period of refeeding was also associated with elevated fasted plasma triglycerides and glucose, significant in NCP groups, suggesting glucose intolerance and possibly insulin resistance. NCP was well-tolerated in healthy young-adults and in malnourished old rats. In healthy adults, NCP at 5 mg/kg/d induced a significant increase in protein content in the soleus, a type I fiber-rich muscle. In malnourished old rats, NCP supply during refeeding, may help to preserve lean mass by limiting protein breakdown; however, these effects may be limited in our model by a possible immediate refeeding-associated glucose intolerance.