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Purpose Obesity is a primary risk factor for knee osteoarthritis (OA). Prebiotics enhance beneficial gut microbes and can reduce body fat and inflammation. Our objective was to examine if a 6-month prebiotic intervention improved physical function in adults with knee osteoarthritis and obesity. We also measured knee pain, body composition, quality of life, gut microbiota, inflammatory markers, and serum metabolomics. Methods Adults (n = 54, mostly women) with co-morbid obesity (BMI > 30 kg/m 2 ) and unilateral/bilateral knee OA were randomly assigned to prebiotic (oligofructose-enriched inulin; 16 g/day; n = 31) or isocaloric placebo (maltodextrin; n = 21) for 6 months. Performance based-tests, knee pain, quality of life, serum metabolomics and inflammatory markers, and fecal microbiota and short-chain fatty acids were assessed. Results Significant between group differences were detected for the change in timed-up-and-go test, 40 m fast paced walk test, and hand grip strength test from baseline that favored prebiotic over placebo. Prebiotic also reduced trunk fat mass (kg) at 6 months and trunk fat (%) at 3 months compared to placebo. There was a trend (p = 0.059) for reduced knee pain at 6 months with prebiotic versus placebo. In gut microbiota analysis, a total of 37 amplicon sequence variants differed between groups. Bifidobacterium abundance was positively correlated with distance walked in the 6-min walk test and hand grip strength. At 6 months, there was a significant separation of serum metabolites between groups with upregulation of phenylalanine and tyrosine metabolism with prebiotic. Conclusion Prebiotics may hold promise for conservative management of knee osteoarthritis in adults with obesity and larger trials are warranted. Clinical Trial Registration Clinicaltrials.gov/study/NCT04172688.

Interactions between the environment, the gut microbiome, and host characteristics that influence bone health are beginning to be explored. This is the first area where functional benefits from diet-induced changes in the gut microbiome have been reported for healthy people. Several prebiotics that reach the lower intestine have resulted in an altered gut microbiome that is thought to enhance fermentation of the fibers to produce short-chain fatty acids. These changes are positively correlated with increases in fractional calcium absorption in adolescents and with increases in measures of bone density and strength in animal models. New methodologies are available to explore mechanisms and to refine intervention strategies.

The ketogenic diet (KD) is an effective treatment for infantile spasms syndrome (IS). However, the KD has implications for somatic growth, development, and the gut microbiota. The impact of incorporating a prebiotic fiber (PRE, oligofructose-enriched inulin, 0.8 g/dL) into a KD diet on spasms, developmental milestones, fecal gut microbiota, metabolites, and hippocampal mitochondrial metabolism were examined. Following IS induction, animals were randomized to KD or KD + PRE diets. A third group without IS and suckled by dams was included as a normally developing reference group (R). PRE inclusion decreased ketones and increased circulating glucose levels but had no impact on spasms. In the liver, PRE increased triglyceride concentrations, decreased carnitine levels, and downregulated genes encoding enzymes responsible for ketogenesis. In the hippocampus, PRE increased glutathione levels but did not affect the maximal respiratory capacity of mitochondria. Analysis of the gut microbiota showed that KD + PRE increased microbial richness and the relative abundance of Bifidobacterium pseudolongum and Lactobacillus johnsonii. No differences in developmental milestones (i.e., surface righting, negative geotaxis, and open field behavior) were observed between KD and KD + PRE, except for ultrasonic vocalizations that were more frequent in KD + PRE. In summary, PRE did not impact spasms or developmental outcomes, but was effective in improving both metabolic parameters and gut microbiota diversity.

There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. Four-week-old wild-type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis-associated colorectal cancer (CRC) was initiated with three 7-day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis. Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.

Background: An inadequate perinatal nutritional environment can alter the maturation of the intestinal barrier and promote long-term pathologies such as metabolic syndrome or chronic intestinal diseases. The intestinal microbiota seems to play a determining role in the development of the intestinal barrier. In the present study, we investigated the impact of consuming an early postnatal prebiotic fiber (PF) on growth, intestinal morphology and the microbiota at weaning in postnatal-growth-restricted mice (PNGR). Methods: Large litters (15 pups/mother) were generated from FVB/NRj mice to induce PNGR at postnatal day 4 (PN4) and compared to control litters (CTRL, 8 pups/mother). PF (a resistant dextrin) or water was orally administered once daily to the pups from PN8 to PN20 (3.5 g/kg/day). Intestinal morphology was evaluated at weaning (PN21) using the ileum and colon. Microbial colonization and short-chain fatty acid (SCFA) production were investigated using fecal and cecal contents. Results: At weaning, the PNGR mice showed decreased body weight and ileal crypt depth compared to the CTRL. The PNGR microbiota was associated with decreased proportions of the Lachnospiraceae and Oscillospiraceae families and the presence of the Akkermansia family and Enterococcus genus compared to the CTRL pups. The propionate concentrations were also increased with PNGR. While PF supplementation did not impact intestinal morphology in the PNGR pups, the proportions of the Bacteroides and Parabacteroides genera were enriched, but the proportion of the Proteobacteria phylum was reduced. In the CTRL pups, the Akkermansia genus (Verrucomicrobiota phylum) was present in the PF-supplemented CTRL pups compared to the water-supplemented ones. Conclusions: PNGR alters intestinal crypt maturation in the ileum at weaning and gut microbiota colonization. Our data support the notion that PF supplementation might improve gut microbiota establishment during the early postnatal period.

Brewer’s spent grain (BSG), the main by-product of the brewing industry, is a rich source of arabinoxylans (AXs) and hydroxycinnamic acids, particularly ferulic acid (FA), which contribute to its prebiotic potential. This study evaluates the prebiotic properties of residual solid from an enzymatically treated BSG, compared to the properties of BSG as a non-enzymatically hydrolyzed control. Although the residual solid exhibited total polyphenol (2581.96 ± 70.63 mg/100 g dry weight) and FA (180.84 ± 3.28 mg/100 g dry weight) contents comparable to those of the non-hydrolyzed control (2500.38 ± 284.20 and 179.59 ± 3.30 mg/100 g dry weight, respectively), the AX content was significantly higher (14,084.81 ± 185.72 mg/100 g), accompanied by a lower degree of feruloylation (12.84 ± 0.23 mg FA/g AX), higher antioxidant activity (64,825.35 ± 4011.24 μmol TE/100 g), and structural changes visualized by scanning electron microscopy. In addition, in vitro colonic fermentation showed a delayed butyrogenic profile, with increased butyrate production compared to the control (3.17 ± 1.44 mM). Microbiota analysis by fluorescence in situ hybridization (FISH) coupled with flow cytometry indicated an increase in butyrate-producing bacteria, including Faecalibacterium prausnitzii (+5.90) and Eubacterium rectale (+6.88). Growth of Bacteroides, Lactobacillus, and Bifidobacterium spp. was also promoted. Overall, these findings suggest that enzymatic processing of BSG can generate a residual solid with modified structural characteristics and potential prebiotic functionality, supporting its potential application as a fermentable flour ingredient in functional foods.

Emerging evidence suggests that low-grade systemic inflammation plays a key role in altering brain activity, behaviour and affect. Modulation of the gut microbiota using prebiotic fibre offers a potential therapeutic tool to regulate inflammation, mediated via the production of short-chain fatty acids (SCFA). However, the impact of prebiotic consumption on affective symptoms and the possible contribution from inflammation, gut symptoms and the gut microbiome are currently underexamined. In this 12-week study, the effects of a diverse prebiotic blend on inflammation, gut microbiota profiles and affective symptoms in a population with metabolic syndrome (MetS) were examined. Sixty males and females with MetS meeting the criteria for MetS were randomised into a treatment group (n 40), receiving 10 g per day of a diverse prebiotic blend and healthy eating advice, and a control group (n 20), receiving healthy eating advice only. Our results showed a significant reduction in high sensitivity C-reactive protein (hs-CRP) in the treatment (–0·58 [–9·96 to–2·63]) compared with control (0·37 [–3·64 to–3·32]), alongside significant improvements in self-reported affective scores in the treatment compared with the control group. While there were no differences in relative abundance between groups at week 12, there was a significant increase from baseline to week 12 in fecal Bifidobacterium and Parabacteroides in the treatment group, both of which are recognised as SCFA producers. Multivariate regression analyses further revealed an association between gastrointestinal symptoms and hs-CRP with affective scores. Together, this study provides preliminary support for a diverse prebiotic blend for mood, stress and anxiety.

Background Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. Methods/design In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks ( n  = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. Discussion There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. Trial registration ClinicalTrials.gov ( NCT02568605 ) Registered 30 September 2015

Background Prosthetic Joint Infection (PJI) is the most devastating complication of arthroplasty surgery and affects 1–5% of patients. Despite strict adherence to aseptic protocols and preventive measures, infection is the most common reason for revision arthroplasty, and the incidence is increasing. Treatment of PJI is challenging and often requires repeated major surgeries with sequentially poor results. The continued occurrence of PJI, and persistence after treatment, brings into question the current treatment paradigm. Preclinical evidence suggests a link between altered gut health and the risk of PJI in arthroplasty patients. Resistant starches helps to restore gut physiology by enhancing the beneficial microbiome and producing short-chain fatty acids, which have several health-conferring properties. The primary aim of this study is to investigate the effect of a commercially available prebiotic fibre formulation on the gut microbiome in PJI patients planned for a two-stage revision surgery. Methods A double-blind placebo-controlled trial will assess the effect of 8-week supplementation of a commercially available prebiotic supplement in patients presenting with first-time PJI undergoing two-stage revision surgery. The supplementation phase will start after the first stage revision, and 80 patients will be randomised to receive either a test product (34 g of resistant starch) or a placebo (custard powder) daily for eight weeks. Stool and blood specimens will be collected at baseline, four weeks and eight weeks after the first-stage surgery and once at second-stage surgery. Gut microbiome profile, inflammatory cytokines and gut permeability biomarkers will be measured. Tissue specimens will be collected intra-operatively during first and second-stage surgeries. Baseline dietary patterns and gut symptoms will be recorded using validated questionnaires. Treatment outcomes will be reported for both cohorts using the Delphi criterion at one and two years after second-stage surgery. Discussion This will be the first study to investigate the relationship between gut health optimisation and preventing PJI recurrence in arthroplasty patients. If supplementation with resistant starch improves gut health and reduces systemic inflammation, optimising the gut microbiome will be a recommended preoperative management strategy for arthroplasty patients. Trial registration no ACTRN12623001273673.

Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (thirty-three) and placebo (thirty-three) interventions. Participants in the treatment arm consumed 20 g/d of a diverse prebiotic fibre supplement, and participants in the placebo arm consumed 2 g/d of cellulose for 24 weeks. A total of fifty-one and forty-eight participants completed the week 16 and week 24 visits, respectively. The intervention was well tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group but only in participants with lower baseline HbA1c levels (< 6 % HbA1c) (P = 0·05; treatment –0·17 ± 0·27 v. placebo 0·07 ± 0·29, mean ± sd). Within the whole cohort, we showed significant improvements in insulin sensitivity (P = 0·03; treatment 1·62 ± 5·79 v. placebo –0·77 ± 2·11) and C-reactive protein (P FWE = 0·03; treatment –2·02 ± 6·42 v. placebo 0·94 ± 2·28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.