Summary Background Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear. Aim The primary aim of this phase I study was to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo while secondary ones were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in MHE patients. Methods Cirrhotic patients with MHE patients were randomized 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed for 8 weeks. Serum, urine and stool samples were collected at baseline and study-end. Safety was assessed at weeks 4 and 8. Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analyzed between groups using correlation networks. Results 30 MHE patients (14 LGG and 16 placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomized group, endotoxemia and TNF-α decreased, microbiome changed (reduced Enterobacteriaceae and increased Clostridiales Incertae Sedis XIV and Lachnospiraceae relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found. Conclusions In this phase I study, LGG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.

No abstract

The patterns of fat distribution and their relationship to severity of nonalcoholic fatty liver disease (NAFLD) are unknown. The objectives of this study were to define the fat distribution patterns and their relationship to histological severity and metabolic parameters in subjects with NAFLD. Anthropometric indices and total body fat were measured in 123 subjects.

These data show that a LCHF diet stimulates PYY secretion more than a LFHC diet in obese individuals.