Objective To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. Design Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. Results Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

A number of bifidobacterial species are found at a particularly high prevalence and abundance in faecal samples of healthy breastfed infants, a phenomenon that is believed to be, at least partially, due to the ability of bifidobacteria to metabolize Human Milk Oligosaccharides (HMOs). In the current study, we isolated a novel strain of Bifidobacterium kashiwanohense, named APCKJ1, from the faeces of a four-week old breastfed infant, based on the ability of the strain to utilise the HMO component fucosyllactose. We then determined the full genome sequence of this strain, and employed the generated data to analyze fucosyllactose metabolism in B. kashiwanohense APCKJ1. Transcriptomic and growth analyses, combined with metabolite analysis, in vitro hydrolysis assays and heterologous expression, allowed us to elucidate the pathway for fucosyllactose metabolism in B. kashiwanohense APCKJ1. Homologs of the key genes for this metabolic pathway were identified in particular in infant-derived members of the Bifdobacterium genus, revealing the apparent niche-specific nature of this pathway, and allowing a broad perspective on bifidobacterial fucosyllactose and L-fucose metabolism.

C-Phycocyanin (CPC) exerts therapeutic, antioxidant, anti-inflammatory and immunomodulatory actions. It prevents oxidative stress and acute kidney damage caused by HgCl₂. However, the exact mechanism of the pharmacological action of C-phycocyanin is as yet unclear. Some proposals express that CPC metabolism releases the active compound phycocyanobilin (PCB) that is able to induce CPC's therapeutical effects as an antioxidant, anti-inflammatory and nephroprotective. This study is aimed to demonstrate that PCB is the molecule responsible for C-phycocyanin's nephroprotective action in the acute kidney injury model caused by HgCl₂. PCB was purified from C-phycocyanin and characterized by spectroscopy and mass spectrometry methods. Thirty-six male mice were administrated with 0.75, 1.5, or 3 mg per kg per d of PCB 30 min before the 5 mg kg⁻¹ HgCl₂ administration. PCB was administered during the following five days, after which the mice were euthanized. Kidneys were dissected to determine oxidative stress and redox environment markers, first-line antioxidant enzymes, effector caspase activities, and kidney damage markers.The quality of purified PCB was evaluated by spectroscopy and mass spectrometry. All PCB doses prevented alterations in oxidative stress markers, antioxidant enzymes, and caspase 9 activities. However, only the dose of 3 mg per kg per d PCB avoided the redox environment disturbance produced by mercury. All doses of PCB partially prevented the down-expression of nephrin and podocin with a consequent reduction in the damage score in a dose-effect manner. In conclusion, it was proven that phycocyanobilin is the molecule responsible for C-phycocyanin's nephroprotective action on acute kidney injury caused by mercury.