Epidemiological studies indicate that chronic obstructive pulmonary disease (COPD) is associated with the incidence of changes in intestinal health. Cigarette smoking, as one of the major causes of COPD, can have an impact on the gastrointestinal system and promotes intestinal diseases. This points to the existence of gut–lung interactions, but an overview of the underlying mechanisms of the bidirectional connection between the lungs and the gut in COPD is lacking. The interaction between the lungs and the gut can occur through circulating inflammatory cells and mediators. Moreover, gut microbiota dysbiosis, observed in both COPD and intestinal disorders, can lead to a disturbed mucosal environment, including the intestinal barrier and immune system, and hence may negatively affect both the gut and the lungs. Furthermore, systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction and play a role in the gut–lung axis. In this review, we summarize data from clinical research, animal models, and in vitro studies that may explain the possible mechanisms of gut–lung interactions associated with COPD. Interesting observations on the possibility of promising future add-on therapies for intestinal dysfunction in patients with COPD are highlighted.

Ischemic stroke is a major cause of death and disability worldwide. There is almost no effective treatment for this disease. Therefore, developing effective treatment for ischemic stroke is urgently needed. Efficient delivery of therapeutic drugs to ischemic sites remained a great challenge for improved treatment of strokes. In recent years, hydrogel-based strategies have been widely investigated for new and improved therapies. They have the advantage of delivering therapeutics in a controlled manner to the poststroke sites, aiming to enhance the intrinsic repair and regeneration. In this review, we discuss the pathophysiology of stroke and the development of injectable hydrogels in the application of both stroke treatment and neural tissue engineering. We also discuss the prospect and the challenges of hydrogels in the treatment of ischemic strokes.

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3′-galactosyl-lactose (3′-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet⁺ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3′-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3′-GL in TOS.

Our objective was to determine the effects of nondigestible oligosaccharides (NDO) on lung health and performance. Three hundred male Holstein-Friesian calves aged 18.0 ± 3.6 d received 1 of 6 treatments for 8.5 wk (period 1). Treatments included a negative control (CON), galacto-oligosaccharides (GOS) administered as a spray via the nose once daily (SPR), GOS administered via the milk replacer (MR) at 1% (GOS-L) and 2% (GOS-H), fructo-oligosaccharides administered via the MR at 0.25% (FOS) and a combination of GOS and fructo-oligosaccharides administered via the MR at 1% and 0.25%, respectively (GOS-FOS). Milk replacer was fed twice daily. Feeding levels were equal between calves and increased progressively in time. Body weight was measured every 4 wk and clinical health was scored weekly. Blood and broncho-alveolar lavage fluid (BALF) samples were collected bi-weekly from a subset of calves (n = 120). After period 1, all calves received the same control MR for 18 wk until slaughter (period 2), during which general performance and clinical health were measured. Generally, infection pressure was high, with clinical scores and BALF proinflammatory TNFα concentrations increasing with time in period 1, which resulted in a high number of required group antimicrobial treatments (6 group antimicrobial treatments in 13 wk, supplied to all calves). Average daily gain adjusted to equal solid feed intake was increased for GOS-L (+61 g/d) compared with CON calves from experimental wk 1 to 5. Plasma white blood cell concentration tended to be lowered by GOS-L, plasma IL-8 concentration was reduced by all orally supplemented NDO, plasma IL-6 was reduced by all NDO treatments except GOS-FOS and plasma IL-1β was reduced by all NDO treatments compared with CON, although this differed per time point for SPR. The neutrophil percentage in BALF was reduced by GOS-L in wk 6, which was associated with a relative increase in macrophages. The BALF concentration of TNFα and IL-8 was reduced or tended to be reduced by GOS-L and GOS-H, while IL-6 was or tended to be reduced by SPR, GOS-L, GOS-H, and GOS-FOS, and IL-1β was reduced by SPR, GOS-L, GOS-H, and FOS. Generally, feeding the combination of GOS and FOS was not more effective than feeding GOS or FOS alone, because feeding GOS-FOS resulted in higher concentrations of plasma and BALF cytokine and chemokine concentrations compared with feeding GOS-L alone, and resulted in higher plasma cytokine concentrations compared with feeding FOS alone. None of the BALF and plasma cytokine or chemokine concentrations differed between the GOS-L and GOS-H treatment. Performance and clinical scores in period 2 did not differ among treatments. Altogether, all tested NDO reduced systemic and lung inflammation in calves under high natural infection pressure and for GOS-fed calves, this increased performance during the first 4 wk. Combining GOS and FOS did not have a synergistic effect. The intranasal administration of GOS also lowered systemic and lung inflammation, but tended to negatively affect performance. Overall, this study demonstrates the potential of NDO to alleviate systemic and respiratory inflammation in calves.

The worldwide increase in the incidence of antibiotic resistance of the atypical bacterium Mycoplasma pneumoniae (MP) challenges the treatment of MP infections, especially in children. Therefore, alternative strategies for the treatment of MP infections are warranted. Galacto- and fructo-oligosaccharides (GOS and FOS) are a specific group of complex carbohydrates that were recently shown to possess direct anti-pathogenic properties. In this study, we assessed whether GOS and FOS exert anti-microbial and anti-infective effects against MP and, especially, macrolide-resistant MP (MRMP) in vitro. The MIC values of GOS for MP and MRMP were 4%. In contrast, the MIC values of FOS for both MP and MRMP were 16%. A time-kill kinetic assay showed that FOS possess bacteriostatic properties, while for GOS, a bactericidal effect against MP and MRMP was observed after 24 h at a concentration of 4x MIC. In co-cultures with human alveolar A549 epithelial cells, GOS killed adherent MP and MRMP and also concentration-dependently inhibited their adherence to A549 cells. Further, GOS suppressed (MR)MP-induced IL-6 and IL-8 in A549 cells. None of the aforementioned parameters were affected when FOS were added to these co-cultures. In conclusion, the anti-infective and anti-microbial properties of GOS could provide an alternative treatment against MRMP and MP infections.

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.