Human Colonic Microbiota and Short-Term Postoperative Outcomes in Colorectal Cancer Patients: A Pilot Study

Despite the advances in surgical techniques and perioperative care, the complication rates after colorectal cancer surgery have remained stable. Recently, it has been suggested that colon microbiota may be implicated in several pathways that can lead to impaired colonic homeostasis and, thereby, to the development of complications after colorectal surgery. The aim of this study was to evaluate the potential impact of colonic dysbiosis on postoperative course. This prospective human clinical study recruited patients operated on for left colon, sigmoid colon or rectal cancer. Colon mucosa and fecal samples were collected to study mucosa associated microbiota (MAM) and luminal microbiota (LM), accordingly. Preliminary analysis for the first 25 consecutive patients with V3–V4 16S rRNA metagenomic analysis was performed. Bacterial composition and abundance in patients who developed postoperative complications over a 90-day follow-up period were compared to those without postoperative complications. Abundance and distribution of genera in MAM differed significantly when compared to LM with a significant impact on neoadjuvant therapy on bacterial composition. Preliminary analysis revealed no statistically significant differences in LM nor in MAM composition when individuals with and without postoperative surgical complications were compared. In cases of postoperative complications, LM and MAM showed significantly decreased diversity. Composition of the colonic microbiota is altered by neoadjuvant therapy. Results on the impact of colonic dysbiosis on postoperative complications are pending the end of the present study, with 50 patients enrolled.

Differential effects of early-life and post-weaning galactooligosaccharides intervention on colonic bacterial composition and function in weaning piglets

Recently, we have proved that the early-life galactooligosaccharides (GOS) intervention could improve the colonic function by altering the bacterial composition in the suckling piglets. However, whether the early-life GOS (ELG) intervention could have a long influence of the colonic microbiota, and the ELG and post-weaning GOS (PWG) combined intervention would have an interaction effect on maintaining colonic health in weaning piglets remain to be explored. Thus in this study, we illustrated the differential effect of ELG and PWG intervention on colonic microbiota and colonic function of weaning piglets. Our results showed that both the ELG and PWG intervention decreased the diarrhea frequency of weaning piglets, while the PWG intervention increased colonic indexes. After 16S rRNA MiSeq sequencing of gut bacteria belonged to colonic niches (mucosa and digesta), the PWG increased the α-diversity of colonic mucosal bacteria was revealed. In addition, we found both the ELG and PWG intervention enriched the abundance of short chain fatty acids (SCFAs) producer in different colonic niches and increased total SCFAs concentrations in colonic digesta. These changes selectively modulated the mRNA expression of pattern recognition receptors and barrier proteins in the colonic mucosa. Of note, the combined effect of ELG and PWG effectively enhanced colonic SCFAs producer enrichment and up-regulated the butyrate concentration. Meanwhile, the gene expression of MyD88-NFκB signaling and the pro-inflammatory cytokines contents were markedly reduced under the combined effect of ELG and PWG. Importance Reducing the disorders of gut ecosystem is an effective way to relieve weaning stresses of piglets and save economic losses in the modern swine industry. To this end, prebiotics were often added in diet during the weaning transition. In present study, we demonstrated that the ELG and PWG intervention had shown different effects on the bacterial composition of different colonic niches and colonic function in the weaning piglets. Especially under the combined effect of ELG and PWG intervention, the gene expression of MyD88-NFκB signaling and the contents of pro-inflammation cytokines decreased with the increasing concentration of butyrate, which is one of the important microbial metabolites in the colon of weaning piglets. These findings further provided new insights into nutritional interventions to alleviate intestinal ecosystem dysbiosis and gut dysfunction in the piglets during the weaning transition.

Spontaneous and Naloxone-Precipitated Withdrawal Behaviors From Chronic Opiates are Accompanied by Changes in N-Oleoylglycine and N-Oleoylalanine Levels in the Brain and Ameliorated by Treatment With These Mediators

Rationale: The endocannabinoidome mediators, N-Oleoylglycine (OlGly) and N-Oleoylalanine (OlAla), have been shown to reduce acute naloxone-precipitated morphine withdrawal affective and somatic responses.Objectives: To determine the role and mechanism of action of OlGly and OlAla in withdrawal responses from chronic exposure to opiates in male Sprague-Dawley rats.Methods: Opiate withdrawal was produced: 1) spontaneously 24 h following chronic exposure to escalating doses of morphine over 14 days (Experiments 1 and 2) and steady-state exposure to heroin by minipumps for 12 days (Experiment 3), 2) by naloxone injection during steady-state heroin exposure (Experiment 4), 3) by naloxone injection during operant heroin self-administration (Experiment 5).Results: In Experiment 1, spontaneous morphine withdrawal produced somatic withdrawal reactions. The behavioral withdrawal reactions were accompanied by suppressed endogenous levels of OlGly in the nucleus accumbens, amygdala, and prefrontal cortex, N-Arachidonylglycerol and OlAla in the amygdala, 2-arachidonoylglycerol in the nucleus accumbens, amygdala and interoceptive insular cortex, and by changes in colonic microbiota composition. In Experiment 2, treatment with OlAla, but not OlGly, reduced spontaneous morphine withdrawal responses. In Experiment 3, OlAla attenuated spontaneous steady-state heroin withdrawal responses at both 5 and 20 mg/kg; OlGly only reduced withdrawal responses at the higher dose of 20 mg/kg. Experiment 4 demonstrated that naloxone-precipitated heroin withdrawal from steady-state exposure to heroin (7 mg/kg/day for 12 days) is accompanied by tissue-specific changes in brain or gut endocannabinoidome mediator, including OlGly and OlAla, levels and colonic microbiota composition, and that OlAla (5 mg/kg) attenuated behavioural withdrawal reactions, while also reversing some of the changes in brain and gut endocannabinoidome and gut microbiota induced by naloxone. Experiment 5 demonstrated that although OlAla (5 mg/kg) did not interfere with operant heroin self-administration on its own, it blocked naloxone-precipitated elevation of heroin self-administration behavior.Conclusion: These results suggest that OlAla and OlGly are two endogenous mediators whose brain concentrations respond to chronic opiate treatment and withdrawal concomitantly with changes in colon microbiota composition, and that OlAla may be more effective than OlGly in suppressing chronic opiate withdrawal responses.

In Vitro Simulation of Human Colonic Fermentation: A Practical Approach towards Models’ Design and Analytical Tools

The human colonic microbiota plays an important role in the food digestion process and has a key role in maintaining health status. This community of microbes is inter-individually different due to several factors that modulate its composition. Among them, diet is one of the most relevant, which, in turn, is affected by environmental, economic, and cultural considerations. These pieces of evidence have promoted the study of the influence of diet on gut microbiota and the development of in vitro models that simulate the colonic digestion of foods. This narrative review aims to present a technical approach of the in vitro gut models available to evaluate the impact of diet on human colonic microbiota. A description and comments on the main characteristics, parameters, applicability, faecal inoculum preparation, and analytical tools are made. Despite the progress of in vitro colonic digestion models and metaomic applicability in this research field, there are still some challenges to face due to the lack of a consensus on the methodologies to conduct in vitro colonic digestions and the need to integrate the metaomic data to fully understand the influence of food in human colonic microbiota.