A Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of (Thetanix) Bacteroides thetaiotaomicron in Adolescent Crohn's Disease.

INTRODUCTION: Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission. METHODS: Subjects who were 16-18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index <12.5) were recruited. Each active dose comprised ∼108.2±1.4 colony forming units of B. thetaiotaomicron (randomized 4:1 active:placebo). Part A was single dose. Part B involved 7.5 days twice daily dosing. Serial stools were analyzed for calprotectin, 16S rRNA sequencing, and B. thetaiotaomicron real-time polymerase chain reaction. Bloods were taken serially. Subjects reported adverse events and recorded temperature twice daily. RESULTS: Fifteen subjects were treated-8 in part A (75% men, median 17.1 years) and 10 in part B, including 3 from part A (80% men, median 17.1 years); all 18 completed. Seventy percent took concurrent immunosuppression. Reported compliance was >99% in part B. Two subjects reported adverse events deemed related-one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4-447] to 50.5 [5.3-572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects. DISCUSSION: Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.

Gut microbiota in older subjects: variation, health consequences and dietary intervention prospects.

Alterations in intestinal microbiota composition and function have been linked to conditions including functional gastrointestinal disorders, obesity and diabetes. The gut microbiome encodes metabolic capability in excess of that encoded by the human genome, and bacterially produced enzymes are important for releasing nutrients from complex dietary ingredients. Previous culture-based studies had indicated that the gut microbiota of older people was different from that of younger adults, but the detailed findings were contradictory. Small-scale studies had also shown that the microbiota composition could be altered by dietary intervention or supplementation. We showed that the core microbiota and aggregate composition in 161 seniors was distinct from that of younger persons. To further investigate the reasons for this variation, we analysed the microbiota composition of 178 elderly subjects for whom the dietary intake data were available. The data revealed distinct microbiota composition groups, which overlapped with distinct dietary patterns that were governed by where people lived: at home, in rehabilitation or in long-term residential care. These diet-microbiota separations correlated with cluster analysis of NMR-derived faecal metabolites and shotgun metagenomic data. Major separations in the microbiota correlated with selected clinical measurements. It should thus be possible to programme the microbiota to enrich bacterial species and activities that promote healthier ageing. A number of other studies have investigated the effect of certain dietary components and their ability to modulate the microbiota composition to promote health. This review will discuss dietary interventions conducted thus far, especially those in elderly populations and highlight their impact on the intestinal microbiota.