Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder.

OBJECTIVE: The gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD. DESIGN: We performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model. RESULTS: ASD and chronological age had the most significant and largest impacts on children's faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum. CONCLUSIONS: Gut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.

OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM). DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24. RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05). CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness. TRIAL REGISTRATION NUMBER: NCT03127696.

Alterations in the Gut Virome in Obesity and Type 2 Diabetes Mellitus.

BACKGROUND & AIMS: Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM. METHODS: There were 128 obese subjects (body mass index ≥28 kg/m2) and 101 lean controls (body mass index ≥18.5 and <23 kg/m2) recruited from 2 regions in China (Hong Kong and Kunming). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome, and viral-bacterial correlations were compared between obese subjects and lean controls. RESULTS: Obese subjects, especially those with T2DM (ObT2), had a decreased gut viral richness and diversity compared with lean controls in the Hong Kong cohort (P < .05), while no significant differences were observed in the Kunming cohort. Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, 17 differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecologic analysis revealed that intensive transkingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (P < .001). CONCLUSIONS: Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Obesity accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that the gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.

Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation.

BACKGROUND & AIMS: Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. METHODS: Proteus spp abundance was assessed by ure gene-specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. RESULTS: Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. CONCLUSIONS: P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study.

BACKGROUND AND AIM: Gut dysbiosis is associated with immune dysfunction and severity of COVID-19. Whether targeting dysbiosis will improve outcomes of COVID-19 is unknown. This study aimed to assess the effects of a novel gut microbiota-derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients. METHODS: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS-CoV-2 viral load, and fecal microbiota profile from admission up to week 5. RESULTS: Twenty-five consecutive COVID-19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS-CoV-2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF-α), and IL-1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS-CoV-2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by week 4 and week 5. CONCLUSIONS: This proof-of-concept study suggested that the use of a novel gut microbiota-derived synbiotic formula, SIM01, hastened antibody formation against SARS-CoV-2, reduced nasopharyngeal viral load, reduced pro-inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID-19 patients.

Adherent-invasive Escherichia coli in inflammatory bowel disease.

Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn's disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.

C-X-C motif chemokine 10 in non-alcoholic steatohepatitis: role as a pro-inflammatory factor and clinical implication.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a more severe form of NAFLD and causes subsequent pathological changes including cirrhosis and hepatocellular carcinoma. Inflammation is the key pathological change in NASH and involves a series of cytokines and chemokines. The C-X-C motif chemokine 10 (CXCL10), which is known as a pro-inflammation chemokine, was recently proven to play a pivotal role in the pathogenesis of NASH. Hepatic CXCL10 is mainly secreted by hepatocytes and liver sinusoidal endothelium. By binding to its specific receptor CXCR3, CXCL10 recruits activated CXCR3+ T lymphocytes and macrophages to parenchyma and promotes inflammation, apoptosis and fibrosis. The circulating CXCL10 level correlates with the severity of lobular inflammation and is an independent risk factor for NASH patients. Thus, CXCL10 may be both a potential prognostic tool and a therapeutic target for the treatment of patients with NASH. The aim of this review is to highlight the growing advances in basic knowledge and clinical interest of CXCL10 in NASH to propagate new insights into novel pharmacotherapeutic avenues.

[Study of genetic polymorphisms of 12 short tandem repeats on X chromosome in ethnic Han population from Hebei Province].

OBJECTIVE: To investigate genetic polymorphisms of 12 X chromosome short tandem repeat (X-STR) loci in ethnic Hebei Han population using an Investigator Argus X-12 amplification kit. METHODS: DNA was extracted for 198 unrelated individuals (96 males and 102 females) and amplified with a fluorescence labeled multiplex PCR system. PCR products were separated and genotyped with capillary array electrophoresis. RESULTS: Only DXS10103 and DXS10101 showed significant linkage disequilibrium at the 12 X-STR loci. One hundred and forty-eight alleles, including 22 off-ladder (OL) alleles, were observed at the 12 X-STR loci in the population. The heterozygosity and polymorphic information content (PIC) were 0.5074-0.9143 and 0.4377-0.9079, respectively. The power of discrimination (PD) was 0.5074-0.9143 in males and 0.6876-0.9863 in females. The mean exclusion chance was 0.4377-0.9079 in the trios cases and 0.2984-0.8373 in the duo cases, respectively. CONCLUSION: The Investigator Argus X12 amplification system is highly polymorphic in ethnic Han population from Hebei and is useful for personal identification and paternity testing.

Input-to-State Stability of Switched Network Control Systems Under Unknown Deception Attacks.

This article focuses on the stability issue of switched network control systems (SNCSs) under deception attacks described by a Bernoulli process with unknown probability distribution. The false information in deception attacks is unknown but bounded and may be state dependent or state independent. By means of the input-to-state stability (ISS) tool and the convex combination method, an improved lemma is first developed for SNCSs, which facilitates the derivations of our results. After that, some attack-independent sufficient conditions for the ISS of SNCSs are obtained for mode-dependent average dwell time switching and stochastic switching, respectively. Different from existing results, the concerned switching contributes to the stability of SNCSs, which benefits the ISS performance of SNCSs even though the unknown deception attacks cause all subsystems to be non-ISS. The proposed results provide an effective solution with strong robustness to deal with unknown deception attacks or denial-of-service attacks.

Alterations in fecal virome and bacteriome virome interplay in children with autism spectrum disorder.

Emerging evidence suggests autism spectrum disorder (ASD) is associated with altered gut bacteria. However, less is known about the gut viral community and its role in shaping microbiota in neurodevelopmental disorders. Herein, we perform a metagenomic analysis of gut-DNA viruses in 60 children with ASD and 64 age- and gender-matched typically developing children to investigate the effect of the gut virome on host bacteria in children with ASD. ASD is associated with altered gut virome composition accompanied by the enrichment of Clostridium phage, Bacillus phage, and Enterobacteria phage. These ASD-enriched phages are largely associated with disrupted viral ecology in ASD. Importantly, changes in the interplay between the gut bacteriome and virome seen in ASD may influence the encoding capacity of microbial pathways for neuroactive metabolite biosynthesis. These findings suggest an impaired bacteriome-virome ecology in ASD, which sheds light on the importance of bacteriophages in pathogenesis and the development of microbial therapeutics in ASD.

Gut mycobiome alterations in obesity in geographically different regions.

The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal - bacterial and fungal - fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p < 0.001), and an improvement in lipid and glucose metabolism compared to mice without intervention. In conclusion, the gut mycobiome composition and functionalities of obese subjects were altered. These data shed light on the potential of utilizing fungus-based therapeutics for the treatment of obesity. S. pombe may serve as a potential fungal probiotic in the prevention of diet-induced obesity and future human trials are needed.

Novel LKF Method on H∞ Synchronization of Switched Time-Delay Systems.

This article investigates H∞ global asymptotic synchronization (GAS) of switched nonlinear systems with delay. By introducing mode-dependent double event-triggering mechanisms (DETMs), the communication resources in both system-controller (S-C) channel and controller-actuator (C-A) channel are saved as much as possible. By designing a new multiple Lyapunov-Krasovskii functional (LKF) with time-varying matrices and developing novel analysis techniques such that the increment of the LKF at switching instant is smaller than one, not only the conservatism of obtained results is greatly reduced but also the nonweighted L2 -gain is convenient to be derived without using any conservative transformation. The exclusion of the Zeno behavior of the DETMs is proved. Synchronization criteria formulated by linear matrix inequalities (LMIs) are given, by which the control gains, event-triggering weights, as well as the minimum L2 -gain are simultaneously designed. Numerical examples demonstrate the low conservatism of the theoretical analysis. Meanwhile, image processing on the basis of the H∞ GAS is provided to further illustrate the perfect performance.

Faecal microbiota transplantations and the role of bacteriophages.

BACKGROUND: Bacteriophages are a major component of the human gut microbiota. Emerging evidence suggests that gut bacteriophages play an important role in the intricate dynamics with bacteria, and their transfer may be associated with the efficacy of faecal microbiota transplantation (FMT). OBJECTIVES: To summarize our current knowledge of the changes in gut bacteriophage communities during FMT and their association with FMT outcome. SOURCES: PubMed, Web of Science, and Google Scholar were searched for articles on FMT and bacteriophages published between May 2013 and January 2022. CONTENT: Preclinical and clinical studies have reported associations between gut bacteriophage profiles and FMT. FMT was associated with donor-specific engraftment of bacteriophages, characterized by increased viral diversity and richness, and the bacteriophage composition resembled the donor's profile after FMT. Limited studies showed that cure after FMT was more likely when an increased fraction of the recipient enteric virome was occupied by donor-derived taxa, including Caudovirales in Clostridioides difficile infection. Faecal virome transplant involving the transfer of the gut virome communities alone may also induce phenotypical and microbiome improvement in various diseases. IMPLICATIONS: The accumulating evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. Better characterization of bacteriophages and an understanding of their underlying mechanisms in FMT are warranted.

Combing fecal microbial community data to identify consistent obesity-specific microbial signatures and shared metabolic pathways.

Obesity is associated with altered gut microbiome composition but data across different populations remain inconsistent. We meta-analyzed publicly available 16S-rRNA sequence datasets from 18 different studies and identified differentially abundant taxa and functional pathways of the obese gut microbiome. Most differentially abundant genera (Odoribacter, Oscillospira, Akkermansia, Alistipes, and Bacteroides) were depleted in obesity, indicating a deficiency of commensal microbes in the obese gut microbiome. From microbiome functional pathways, elevated lipid biosynthesis and depleted carbohydrate and protein degradation suggested metabolic adaptation to high-fat, low-carbohydrate, and low-protein diets in obese individuals. Machine learning models trained on the 18 studies were modest in predicting obesity with a median AUC of 0.608 using 10-fold cross-validation. The median AUC increased to 0.771 when models were trained in eight studies designed for investigating obesity-microbiome association. By meta-analyzing obesity-associated microbiota signatures, we identified obesity-associated depleted taxa that may be exploited to mitigate obesity and related metabolic diseases.

A Probiotic Formula for Modulation of Colorectal Cancer Risk via Reducing CRC-Associated Bacteria.

Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development.

Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea.

BACKGROUND: Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS). AIM: We performed a randomised trial to assess the efficacy of FMT in patients with IBS. METHODS: We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT. RESULTS: At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT. CONCLUSION: FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).

A novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer.

Chemotherapy is the first choice for the treatment of cancer but it is still limited by insufficient kill efficiency and drug resistance. These problems urgently need to be overcome in a way that minimizes damage to the body. In this study, we designed the nanocomposite microparticles (NMPs) modified by cetuximab (Cet) and loaded anti-tumor agents- quercetin (QUE) and paclitaxel (PTX)- for eliciting specific drugs homing and enhancing the killing efficiency of chemotherapy drugs (P/Q@CNMPs). Physicochemical characteristics results presented that P/Q@CNMPs have a suitable aerodynamic diameter and uniform morphology that could meet the requirements of particles deposition in the lung. And it also had the characteristics of sustained-release and pH-responsive which could release the agents in the right place and has a continuous effect. In vitro and in vivo analysis results presented that P/Q@CNMPs have the accuracy targeting ability and killing effect on non-small cell lung cancer (NSCLC) which express positive epidermal growth factor receptor (EGFR) on the membrane. Furthermore, this system also has low toxicity and good biocompatibility. These results demonstrated that P/Q@CNMPs could be a potential intelligent targeting strategy used for chemo-resistant NSCLC therapies.

Gut microbiota in patients with obesity and metabolic disorders - a systematic review.

BACKGROUND: Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic disorders. We performed a systematic review to explore evidence for this association across different geography and populations. METHODS: We performed a systematic search of MEDLINE (OvidSP) and Embase (OvidSP) of articles published from Sept 1, 2010, to July 10, 2021, for case-control studies comparing intestinal microbiome of individuals with obesity and metabolic disorders with the microbiome of non-obese, metabolically healthy individuals (controls). The primary outcome was bacterial taxonomic changes in patients with obesity and metabolic disorders as compared to controls. Taxa were defined as "lean-associated" if they were depleted in patients with obesity and metabolic disorders or negatively associated with abnormal metabolic parameters. Taxa were defined as "obesity-associated" if they were enriched in patients with obesity and metabolic disorders or positively associated with abnormal metabolic parameters. RESULTS: Among 2390 reports screened, we identified 110 full-text articles and 60 studies were included. Proteobacteria was the most consistently reported obesity-associated phylum. Thirteen, nine, and ten studies, respectively, reported Faecalibacterium, Akkermansia, and Alistipes as lean-associated genera. Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated genus in the West. CONCLUSIONS: We identified specific bacteria associated with obesity and metabolic disorders in western and eastern populations. Mechanistic studies are required to determine whether these microbes are a cause or product of obesity and metabolic disorders.