The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

An obesity-associated gut microbiome with increased capacity for energy harvest

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.

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Obesity alters gut microbial ecology

The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial. We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ.

https://science.sciencemag.org/content/sci/307/5717/1915.full.pdf

Host-Bacterial Mutualism in the Human Intestine

Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time — especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.

/pdf/diversity-stability-and-resilience-of-the-human-gut-2sktyw2s6e.pdf

Diversity, stability and resilience of the human gut microbiota

The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.

/pdf/interactions-between-the-microbiota-and-the-immune-system-4m288f09c3.pdf

Interactions between the microbiota and the immune system.

Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on food particles and mucus, selectively induced outer-membrane polysaccharide-binding proteins and glycoside hydrolases, prioritized the consumption of liberated hexose sugars, and revealed a capacity to turn to host mucus glycans when polysaccharides were absent from the diet. This flexible foraging behavior should contribute to ecosystem stability and functional diversity.

https://science.sciencemag.org/content/sci/307/5717/1955.full.pdf

Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont

Abstract Background and Aim Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion. Methods Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively. The primary outcome was the rate of infusion reactions. Secondary outcomes were assessment of the effect of premedications and immunomodulators on the rate of infusion reactions, and cost-effectiveness analysis. The cost-effectiveness analysis was based on direct nursing costs for the infusion time, indirect infusion center costs, and cost of productivity loss for patients. This trial is registered with ClinicalTrials.gov, NCT05340764. Results From November 2020 to November 2021, 96 patients were randomly assigned: 51 (53%) to the 1-hour infusion group and 45 (47%) to the 2-hour infusion group. Over a median time of 1 year, 309 infusions were administered in the control group, and 376 in the study group. Fifty-seven (18%) infusions in the control group and 45 (12%) infusions in the study group experienced an infusion reaction. The only infusion reaction was asymptomatic hypotension not requiring infusion discontinuation. No other infusion reactions (mild or moderate/severe) were seen. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18–3.52], P = .01). The average costs were estimated to reduce by 37% in the accelerated infusion group. Conclusions Accelerated 1-hour infusions are non-inferior in safety and superior in cost-effectiveness compared with standard 2-hour infusions in IBD patients receiving maintenance infliximab infusions. Trial Identification Number Registered with ClinicalTrials.gov, NCT05340764.

/pdf/accelerated-infliximab-infusion-safety-and-tolerability-is-1m23bctt.pdf

Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study

Chien-Huan Chen

Papers

Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont

Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study

Recurrent foreign body ingestion in individuals with psychiatric diagnoses is associated with high rates of healthcare utilization

390 enabling tobacco treatment for gastroenterology patients via a novel low-burden point-of-care model

Tu1456: TAUROURSODEOXYCHOLIC ACID (TUDCA) REDUCES ER STRESS AND CLINICAL DISEASE ACTIVITY IN ULCERATIVE COLITIS: FINAL RESULTS OF A PHASE I TRIAL