Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

Moraxella-dominated pediatric nasopharyngeal microbiota associate with upper respiratory infection and sinusitis.

BACKGROUND: Distinct bacterial upper airway microbiota structures have been described in pediatric populations, and relate to risk of respiratory viral infection and, exacerbations of asthma. We hypothesized that distinct nasopharyngeal (NP) microbiota structures exist in pediatric populations, relate to environmental exposures and modify risk of acute sinusitis or upper respiratory infection (URI) in children. METHODS: Bacterial 16S rRNA profiles from nasopharyngeal swabs (n = 354) collected longitudinally over a one-year period from 58 children, aged four to seven years, were analyzed and correlated with environmental variables, URI, and sinusitis outcomes. RESULTS: Variance in nasopharyngeal microbiota composition significantly related to clinical outcomes, participant characteristics and environmental exposures including dominant bacterial genus, season, daycare attendance and tobacco exposure. Four distinct nasopharyngeal microbiota structures (Cluster I-IV) were evident and differed with respect to URI and sinusitis outcomes. These clusters were characteristically either dominated by Moraxella with sparse underlying taxa (Cluster I), comprised of a non-dominated, diverse microbiota (Cluster II), dominated by Alloiococcus/Corynebacterium (Cluster III), or by Haemophilus (Cluster IV). Cluster I was associated with increased risk of URI and sinusitis (RR = 1.18, p = 0.046; RR = 1.25, p = 0.009, respectively) in the population studied. CONCLUSION: In a pediatric population, URI and sinusitis associate with the presence of Moraxella-dominated NP microbiota.

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis. METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing. RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance. CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis.

Microbial dysbiosis commonly occurs in patients with inflammatory bowel diseases (IBD). Exogenous causes of dysbiosis such as antibiotics and diet are well described, but host derived causes are understudied. A20 is a potent regulator of signals triggered by microbial pattern molecules, and A20 regulates susceptibility to intestinal inflammation in mice and in humans. We now report that mice lacking A20 expression in dendritic cells, A20FL/FL CD11c-Cre mice (or A20dDC mice), spontaneously develop colitogenic intestinal dysbiosis that is evident upon weaning and precedes the onset of colitis. Intestines from A20dDC mice express increased amounts of Reg3ß and Reg3γ, but not Ang4. A20 deficient DCs promote gut microbiota perturbation in the absence of adaptive lymphocytes. Moreover, A20 deficient DCs directly induce expression of Reg3ß and Reg3γ but not Ang 4 in normal intestinal epithelial cell enteroid cultures in the absence of other cell types. These findings reveal a pathophysiological pathway in which defective expression of an IBD susceptibility gene in DCs drives aberrant expression of anti-bacterial peptides and luminal dysbiosis that in turn confers host susceptibility to intestinal inflammation.

Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile.

Background: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD). Objective: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT. Methods: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT. Results: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota. Conclusions: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.