The high-refined carbohydrate diet (HC diet) is linked to anxiety development and oxidative damage to heart tissue. However, little is known about how the gut microbiota profile is modulated in this diet model. Minocycline is an antibiotic with anti-inflammatory, antioxidant, and matrix metalloproteinases (MMPs) inhibitor properties. Therefore, we evaluated the effects of minocycline treatment on HC diet-induced cardiac damage, anxiety-like behaviour, and bacterial gut dysbiosis in mice. Male BALB/C mice were divided into two groups, which received standard diet or HC diet for 12 weeks. In the 10th week, both groups were subdivided and received water or minocycline (50 mg/kg) by gavage for 15 days. The gut bacterial populations, behavioural parameters, adiposity index, biochemical profile, cardiac oxidative stress indicators, MMPs, cardiac remodelling, and contractile analyses by Langendorff-perfused hearts were analysed. The HC diet induced bacterial gut dysbiosis and anxiety-like behaviour increased the adiposity index with changes in the lipid profile and creatine kinase fraction MB (CK-MB). In the heart, the HC diet increased tissue oxidative stress, MMP-2 and MMP-9 activity, collagen deposition, and altered cardiac performance. Minocycline treatment reversed diet-induced bacterial gut dysbiosis and anxiety-like behaviour, ameliorated the biochemical profile, diminished oxidative stress, MMP activity, cardiac collagen deposition, and improved cardiac performance. These findings suggest that minocycline treatment modulated the microbiota and attenuated behavioural changes and cardiac damage caused by the HC diet, suggesting an interplay between the gut-microbiota-brain axis and cardiac damage caused by the HC diet consumption.

Numerous physiological responses to exercise are observed in humans, yet the effects of long-term exercise and varying intensities on the diversity and composition of human fecal microbiota remain unclear. We investigated the effect of a 24-week supervised concurrent exercise intervention, at moderate and vigorous intensities, on fecal microbiota diversity and composition in young adults.

This ancillary study was based on data from the ACTIBATE randomized controlled trial (ClinicalTrials.gov ID: NCT02365129), and included adults (aged 18-25 years, 70 % female) that were randomized to (i) a control group (CON: no exercise, n = 20), (ii) a moderate-intensity exercise group (MOD-EX, n = 21), and (iii) a vigorous-intensity exercise group (VIG-EX, n = 20). Fecal samples were collected before and after the 24-week exercise intervention, and the diversity and composition of the fecal microbiota were analyzed by 16S rRNA sequencing. Inferential functional profiling of the fecal microbiota was performed and correlations between microbial changes and cardiometabolic outcomes were assessed.

Exercise did not modify beta or alpha diversities regardless of the intensity (all P ≥ 0.062). The relative abundance of the Erysipelotrichaceae family (Bacillota phylum) (-0.3 ± 1.2 %; P = 0.031) was however reduced in the VIG-EX group. Coprococcus was the only genus showed a significant difference between MOD-EX and VIG-EX after the intervention, with its relative abundance increasing in MOD-EX (+0.4 ± 0.6 %; P = 0.005). None of these changes were related to the exercise-induced cardiometabolic benefits (all P ≥ 0.05).

In young adults, a 24-week supervised concurrent exercise program, at moderate and vigorous intensities, resulted in minor changes in fecal microbiota composition, while neither alpha nor beta diversities were affected.

ClinicalTrials.gov ID: NCT02365129.

Sucrose-rich diets promote hepatic de novo lipogenesis (DNL) and steatosis through interactions with the gut microbiota. However, the role of sugar-microbiota dynamics in the absence of dietary fat remains unclear. This study aimed to investigate the effects of a high-sucrose, zero-fat diet (ZFD) on hepatic steatosis and host metabolism in conventionally raised (CONVR) and germ-free (GF) mice.

CONVR and GF mice were fed a ZFD, and hepatic lipid accumulation, gene expression, and metabolite levels were analyzed. DNL activity was assessed by measuring malonyl-CoA levels, expression of key DNL enzymes, and activation of the transcription factor SREBP-1c. Metabolomic analyses of portal vein plasma identified microbiota-derived metabolites linked to hepatic steatosis. To further examine the role of SREBP-1c, its hepatic expression was knocked down using antisense oligonucleotides in CONVR ZFD-fed mice.

The gut microbiota was essential for sucrose-induced DNL and hepatic steatosis. In CONVR ZFD-fed mice, hepatic fat accumulation increased alongside elevated expression of genes encoding DNL enzymes, higher malonyl-CoA levels, and upregulation of SREBP-1c. Regardless of microbiota status, ZFD induced fatty acid elongase and desaturase gene expression and increased hepatic monounsaturated fatty acids. Metabolomic analyses identified microbiota-derived metabolites associated with hepatic steatosis. SREBP-1c knockdown in CONVR ZFD-fed mice reduced hepatic steatosis and suppressed fatty acid synthase expression.

Sucrose-microbiota interactions and SREBP-1c are required for DNL and hepatic steatosis in the absence of dietary fat. These findings provide new insights into the complex interplay between diet, gut microbiota, and metabolic regulation.

Dietary prebiotics pectin and resistant starch type-4 (RS-4) promote satiety and alter gut microbiota; however, the underlying neurohormonal mechanisms of satiety remain poorly understood. We determined the effects of pectin, RS-4, and their combination on energy balance and gut microbiota composition, and assessed whether the gut hormones peptide YY (PYY) and cholecystokinin (CCK) play a role in fiber-induced satiety. High-fat diet -induced obese male rats (n = 7-8/group) were fed either control, pectin, RS-4, or a combination of pectin and RS-4 diet. We found that pectin, RS-4, and their combination decreased food intake. Pectin alone, or combined with RS-4, shifted substrate utilization towards fat and reduced gains in weight and adiposity. Pectin alone or combined with RS-4 enhanced the expression and plasma concentrations of PYY and CCK. Importantly, systemic blockade of PYY-Y2 and CCK-1 receptors attenuated the hypophagic effects of pectin, and CCK-1 receptor blockade partly attenuated the hypophagia from RS-4. The prebiotics significantly altered fecal β-diversity metrics, suggestive of improvements in gut microbiota composition. Pectin and RS-4 alone, or in combination, were associated with increased relative abundance of phylum Bacteroidota, decreased Firmicutes, and increased concentrations of amino acids and biogenic amines in feces. Collectively, these findings suggest that dietary pectin and RS-4 improved energy balance and gut microbiota composition, and importantly, demonstrated that the satiety effects of these diets were mediated, in part, via enhanced endogenous PYY and CCK signaling.

Limited studies have addressed the effects of multi-strain probiotics on gut microbiota and their influence on meat traits in pigs. Thus, this study investigated the impact of including a commercialized multi-strain probiotic product (SYN) (SYNLAC-LeanAd) into the dietary regimen of crossbred Landrace × Yorkshire × Duroc (LYD) pigs. The study spanned a duration of 22 weeks, from weaning until slaughtering, during which the carcass traits, meat quality, and fecal microbiota profile were compared to those of pigs fed diets with or without an antibiotic growth promoter (AGP). The results demonstrated that the inclusion of SYN significantly improved meat quality parameters, including marbling score, tenderness, and intramuscular fat (p < 0.05) in comparison to pigs fed with AGP. The analysis of fecal microbiota revealed that SYN inclusion increased the populations of Clostridiaceae, Coriobacteriaceae, and Erysipelotrichaceae compared to the control and AGP groups. Additionally, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis predicted that the amino acid and lipid metabolism pathways were facilitated in pigs from the SYN group. These findings suggest that the inclusion of SYNLAC-LeanAd has the potential to positively impact the fecal microbiota profile, which in turn may lead to improved carcass traits and meat quality in commercial crossbred pigs.

Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.

Diet has a pivotal role in shaping the composition, function and diversity of the gut microbiome, with various diets having a profound impact on the stability, functionality and diversity of the microbial community within our gut. Understanding the profound impact of varied diets on the microbiome is crucial, as it will enable us not only to make well-informed dietary decisions for better metabolic and intestinal health, but also to prevent and slow the onset of specific diet-related diseases that stem from suboptimal diets. In this Review, we explore how geographical location affects the gut microbiome and how different diets shape its composition and function. We examine the mechanisms by which whole dietary regimes, such as the Mediterranean diet, high-fibre diet, plant-based diet, high-protein diet, ketogenic diet and Western diet, influence the gut microbiome. Furthermore, we underscore the need for exhaustive studies to better understand the causal relationship between diet, host and microorganisms for the development of precision nutrition and microbiome-based therapies.

The gut microbiota begins to colonize the host body following birth, develops during the suckling period and changes to the adult type after weaning. The early gut microbiota during the suckling period is thought to have profound effects on the host physiology throughout life but it is still unclear whether early dysbiosis is retained lifelong. Our previous study indicated that chronic nasal inflammation induces dysbiosis of gut microbiota in adult mice. In the present study, we addressed the question as to whether early exposure to chronic nasal inflammation induces dysbiosis, and if so, whether the dysbiosis is retained until adulthood and the sex differences in this effect. Male and female mice received repeated intranasal administration of lipopolysaccharide (LPS) or saline twice a week from P7 to P24 and were weaned at P24. The cecal contents were obtained for 16S rRNA analysis at 2 time points: at 4 weeks (wks), just after weaning, and at maturation to adulthood at 10 wks. The body weight did not differ between saline- and LPS-treated mice till around weaning, suggesting that the mothers' milk was given similarly to all mice. At 4 wks, the beta diversity was significantly different between saline- and LPS-treated male and female mice and the composition of the gut microbiota changed in LPS-treated mice. The abundance of phylum Bacteroidota tended to decrease and that of Firmicutes increased in LPS-treated male mice, while the abundance of Deferribacterota increased in LPS-treated female mice. At 10 wks, the beta diversity was not different between saline- and LPS-treated mice, but the abundance of family Lachnospiraceae significantly decreased in LPS-treated male and female mice by LEfSe analysis. Together, chronic nasal inflammation early in life caused transient and long-term dysbiosis of gut microbiota, which may contribute to the onset and progress of metabolic and neuropsychiatric disorders.

The importance of early microbial dysbiosis in later development of obesity and metabolic disorders has been a subject of debate. Here we tested cause and effect in mice.

Germ-free male Swiss Webster mice were colonized in a specific-pathogen-free (SPF) facility at 1 week (1W) and 3 weeks (3W) of age. They were challenged with a high-fat diet and their responses were compared with SPF mice. Gut microbiota was analyzed by 16S rRNA gene sequencing. Moreover, RNA sequencing of the liver was performed on additional 3W and SPF mice on a regular chow diet.

There were no significant differences in weight, food consumption, epididymal fat weight, HbA1c levels, and serum insulin and leptin, whereas the early germ-free period resulted in mice with impaired glucose tolerance. Both the 1W and 3W group peaked 56% (p < 0.05) and 66% (p < 0.01) higher in blood glucose than the SPF control group, respectively. This was accompanied by a 45% reduction in the level of the anti-inflammatory cytokine IL-10 in the 1W mice (p < 0.05). There were no differences in the gut microbiota between the groups, indicating that all mice colonized fully after the germ-free period. Marked effects on hepatic gene expression (728 differentially expressed genes with adjusted p < 0.05 and a fold change ± 1.5) suggested a potential predisposition to a higher risk of developing insulin resistance in the 3W group.

Lack of microbes early in life had no impact on adiposity but led to insulin resistance and altered liver gene expression related to glucose metabolism in mice. The study strongly supports the notion that microbial signaling to the liver in the beginning of life can alter the host's risk of developing metabolic disorder later in life.

Over the past 40 years, the prevalence of obesity has risen dramatically, reaching epidemic proportions. By 2030 the number of people affected by obesity will reach 1.12 billion worldwide. Gastrointestinal hormones, namely incretins, play a vital role in the pathogenesis of obesity and its comorbidities. GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1), which are secreted from the intestine after nutrient intake and stimulate insulin secretion from pancreatic β cells, influence lipid metabolism, gastric empting, appetite and body weight. The gut microbiota plays an important role in various metabolic conditions, including obesity and type 2 diabetes and influences host metabolism through the interaction with enteroendocrine cells that modulate incretins secretion. Gut microbiota metabolites, such as short-chain fatty acids (SCFAs) and indole, directly stimulate the release of incretins from colonic enteroendocrine cells influencing host satiety and food intake. Moreover, bariatric surgery and incretin-based therapies are associated with increase gut bacterial richness and diversity. Understanding the role of incretins, gut microbiota, and their metabolites in regulating metabolic processes is crucial to develop effective strategies for the management of obesity and its associated comorbidities.

The gut microbiota contributes to metabolic diseases, such as diabetes and hypertension, but is poorly characterized in chronic kidney disease (CKD).

We enrolled 24 adults within household pairs, in which at least one member had self-reported kidney disease, diabetes, or hypertension. CKD was classified based on estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine-albumin-to-creatinine ratio of ≥ 30 mg/g. Participants collected stool and dietary recalls seasonally over a year. Gut microbiota was characterized using 16s rRNA and metagenomic sequencing.

Ten participants had CKD (42%) with a median (interquartile range) estimated glomerular filtration rate of 49 (44, 54) mL/min/1.73 m2. By 16s rRNA sequencing, there was moderate to high intraclass correlation (ICC = 0.63) for seasonal alpha diversity (Shannon index) within individuals and modest differences by season (P < .01). ICC was lower with metagenomics, which has resolution at the species level (ICC = 0.26). There were no differences in alpha or beta diversity by CKD with either method. Among 79 genera, Frisingicoccus, Tuzzerella, Faecalitalea, and Lachnoclostridium had lower abundance in CKD, while Collinsella, Lachnospiraceae_ND3007, Veillonella, and Erysipelotrichaceae_UCG_003 were more abundant in CKD (each nominal P < .05) using 16s rRNA sequencing. Higher Collinsella and Veillonella and lower Lachnoclostridium in CKD were also identified by metagenomics. By metagenomics, Coprococcus catus and Bacteroides stercoris were more and less abundant in CKD, respectively, at false discovery rate corrected P = .02.

We identified candidate taxa in the gut microbiota associated with CKD. High ICC in individuals with modest seasonal impacts implies that follow-up studies may use less frequent sampling.

We employed Mendelian randomization (MR) analysis to investigate the causal relationship between the gut microbiota, acute pancreatitis, and potential inflammatory proteins.

The data for gut microbiota, acute pancreatitis, and inflammatory proteins are sourced from public databases. We conducted a bidirectional MR analysis to explore the causal relationship between gut microbiota and acute pancreatitis, and employed a two-step MR analysis to identify potential mediating inflammatory proteins. IVW is the primary analysis method, heterogeneity, pleiotropy, and sensitivity analyses were also conducted simultaneously.

We identified five bacterial genera associated with the risk of acute pancreatitis, namely genus.Coprococcus3, genus.Eubacterium fissicatena group, genus.Erysipelotrichaceae UCG-003, genus.Fusicatenibacter, and genus.Ruminiclostridium6. Additionally, we have discovered three inflammatory proteins that are also associated with the occurrence of acute pancreatitis, namely interleukin-15 receptor subunit alpha (IL-15RA), monocyte chemoattractant protein-4 (CCL13), and tumor necrosis factor receptor superfamily member 9 (TNFRSF9). Following a two-step MR analysis, we ultimately identified IL-15RA as a potential intermediate factor, with a mediated effect of 0.018 (95% CI: 0.005 - 0.032).

Our results support the idea that genus.Coprococcus3 promotes the occurrence of acute pancreatitis through IL-15RA. Furthermore, there is a potential causal relationship between the gut microbiota, inflammatory proteins, and acute pancreatitis. These findings provide new insights for subsequent acute pancreatitis prevention.

Emerging evidence suggests that maternal obesity negatively impacts the health of offspring. Additionally, obesity is a risk factor for hepatocellular carcinoma (HCC). Our study aims to investigate the impact of maternal obesity on the risk for HCC development in offspring and elucidate the underlying transmission mechanisms.

Female mice were fed either a high-fat diet (HFD) or a normal diet (ND). All offspring received a ND after weaning. We studied liver histology and tumor load in a N-diethylnitrosamine (DEN)-induced HCC mouse model.

Maternal obesity induced a distinguishable shift in gut microbial composition. At 40 weeks, female offspring of HFD-fed mothers (HFD offspring) were more likely to develop steatosis (9.43% vs. 3.09%, p = 0.0023) and fibrosis (3.75% vs. 2.70%, p = 0.039), as well as exhibiting an increased number of inflammatory infiltrates (4.8 vs. 1.0, p = 0.018) and higher expression of genes involved in fibrosis and inflammation, compared to offspring of ND-fed mothers (ND offspring). A higher proportion of HFD offspring developed liver tumors after DEN induction (79.8% vs. 37.5%, p = 0.0084) with a higher mean tumor volume (234 vs. 3 μm3, p = 0.0041). HFD offspring had a significantly less diverse microbiota than ND offspring (Shannon index 2.56 vs. 2.92, p = 0.0089), which was rescued through co-housing. In the principal component analysis, the microbiota profile of co-housed animals clustered together, regardless of maternal diet. Co-housing of HFD offspring with ND offspring normalized their tumor load.

Maternal obesity increases female offspring's susceptibility to HCC. The transmission of an altered gut microbiome plays an important role in this predisposition.

The worldwide incidence of obesity is constantly rising, with more and more children born to obese mothers. In this study, we investigate the impact of maternal diet on gut microbiome composition and its role in liver cancer development in offspring. We found that mice born to mothers with a high-fat diet inherited a less diverse gut microbiome, presented chronic liver injury and an increased risk of developing liver cancer. Co-housing offspring from normal diet- and high-fat diet-fed mothers restored the gut microbiome and, remarkably, normalized the risk of developing liver cancer. The implementation of microbial screening and restoration of microbial diversity holds promise in helping to identify and treat individuals at risk to prevent harm for future generations.

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.

Overweight and obesity are characterized by excessive fat mass accumulation produced when energy intake exceeds energy expenditure. One plausible way to control energy expenditure is to modulate thermogenic pathways in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Among the different environmental factors capable of influencing host metabolism and energy balance, the gut microbiota is now considered a key player. Following pioneering studies showing that mice lacking gut microbes (that is, germ-free mice) or depleted of their gut microbiota (that is, using antibiotics) developed less adipose tissue, numerous studies have investigated the complex interactions existing between gut bacteria, some of their membrane components (that is, lipopolysaccharides), and their metabolites (that is, short-chain fatty acids, endocannabinoids, bile acids, aryl hydrocarbon receptor ligands and tryptophan derivatives) as well as their contribution to the browning and/or beiging of WAT and changes in BAT activity. In this Review, we discuss the general physiology of both WAT and BAT. Subsequently, we introduce how gut bacteria and different microbiota-derived metabolites, their receptors and signalling pathways can regulate the development of adipose tissue and its metabolic capacities. Finally, we describe the key challenges in moving from bench to bedside by presenting specific key examples.

This study aimed to determine the effects of different energy loads on the gut microbiota composition and the rates of energy and nutrient excretion via feces and urine.

A randomized crossover dietary intervention study was conducted with three dietary conditions: overfeeding (OF), control (CON), and underfeeding (UF). Ten healthy men were subjected to each condition for 8 days (4 days and 3 nights in nonlaboratory and laboratory settings each). The effects of dietary conditions on energy excretion rates via feces and urine were assessed using a bomb calorimeter.

Short-term energy loads dynamically altered the gut microbiota at the α-diversity (Shannon index), phylum, and genus levels (p < 0.05). Energy excretion rates via urine and urine plus feces decreased under OF more than under CON (urine -0.7%; p < 0.001, urine plus feces -1.9%; p = 0.049) and UF (urine -1.0%; p < 0.001, urine plus feces -2.1%; p = 0.031). However, energy excretion rates via feces did not differ between conditions.

Although short-term overfeeding dynamically altered the gut microbiota composition, the energy excretion rate via feces was unaffected. Energy excretion rates via urine and urine plus feces were lower under OF than under CON and UF conditions.

The aim of this study was to investigate the impact of dietary nicotinic acid (NA) on apparent nutrient digestibility, rumen fermentation, and rumen microbiota in uncastrated Xiangzhong black cattle.

Twenty-one uncastrated Xiangzhong black cattle (385.08±15.20 kg) aged 1.5 years were randomly assigned to the control group (CL, 0 mg/kg NA in concentrate diet), NA1 group (800 mg/kg NA in concentrate diet) and NA2 group (1,200 mg/kg NA in concentrate diet). All animals were fed a 60% concentrate diet and 40% dried rice straw for a 120-day feeding experiment.

Supplemental NA not only enhanced the apparent nutrient digestibility of acid detergent fiber (p<0.01), but also elevated the rumen acetate and total volatile fatty acid concentrations (p<0.05). 16S rRNA gene sequencing analysis of rumen microbiota revealed that dietary NA changed the diversity of rumen microbiota (p<0.05) and the abundance of bacterial taxa in the rumen. The relative abundances of eight Erysipelotrichales taxa, five Ruminococcaceae taxa, and five Sphaerochaetales taxa were decreased by dietary NA (p< 0.05). However, the relative abundances of two taxa belonging to Roseburia faecis were increased by supplemental 800 mg/kg NA, and the abundances of seven Prevotella taxa, three Paraprevotellaceae taxa, three Bifidobacteriaceae taxa, and two operational taxonomic units annotated to Fibrobacter succinogenes were increased by 1,200 mg/kg NA in diets. Furthermore, the correlation analysis found significant correlations between the concentrations of volatile fatty acids in the rumen and the abundances of bacterial taxa, especially Prevotella.

The results from this study suggest that dietary NA plays an important role in regulating apparent digestibility of acid detergent fiber, acetate, total volatile fatty acid concentrations, and the composition of rumen microbiota.

The composition and function of the intestinal microbiota are major determinants of human health and are strongly influenced by diet, antibiotic treatment, lifestyle and geography. Nevertheless, we currently have only little data on microbiomes of non-westernized communities. We assess the stool microbiota composition in 59 children aged 2-5 years from the Adadle district of Ethiopia, Somali Regional State. Here, milk and starch-rich food are predominant components of the local diet, where the inhabitants live a remote, traditional agropastoral lifestyle. Microbiota composition, function and the resistome were characterized by both 16S rRNA gene amplicon and shotgun metagenomic sequencing and compared to 1471 publicly available datasets from children living in traditional, transitional, and industrial communities with different subsistence strategies. Samples from the Adadle district are low in Bacteroidaceae, and Prevotellaceae, the main bacterial representatives in the feces of children living in industrialized and non-industrialized communities, respectively. In contrast, they had a higher relative abundance in Streptococcaceae, Bifidobacteriaceae and Erysipelatoclostridiaceae. Further, genes involved in degradation pathways of lactose, D-galactose and simple carbohydrates were enriched. Overall, our study revealed a unique composition of the fecal microbiota of these agropastoral children, highlighting the need to further characterize the fecal bacterial composition of human populations living different lifestyles.

Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.

The role of the gut microbiota in determining body fatness has been a prominent area of research and has received significant public attention. Based largely on animal studies, recent attempts to translate these findings into interventions in humans have not been successful. This review will outline the key mouse research that initiated this area of study, examine whether those results warranted the initial enthusiasm and progress into human studies, and examine whether later follow-up research supported earlier conclusions. It will look at whether the absence of a gut microbiota protects germ-free mice from obesity, whether microbiota can transfer obesity into germ-free mice, the evidence for the role of immune system activation as a causal mechanism linking the gut microbiota to body weight, and consider the evidence for effects of individual bacterial species. Finally, it will examine the outcomes of randomized controlled trials of microbiota transfer in human participants that have not shown effects on body weight. With a more critical reading, early studies did not show as large an effect as first appeared and later research, including human trials, has failed to support a role of the gut microbiota in shaping body weight. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

The continued global increase in the prevalence of obesity prompted a meeting at the Royal Society of London investigating causal mechanisms of the disease, 'Causes of obesity: theories, conjectures, and evidence' in October 2022. Evidence presented indicates areas of obesity science where there have been advancements, including an increased understanding of biological and physiological processes of weight gain and maintenance, yet it is clear there is still debate on the relative contribution of plausible causes of the modern obesity epidemic. Consensus was reached that obesity is not a reflection of diminished willpower, but rather the confluence of multiple, complex factors. As such, addressing obesity requires multifactorial prevention and treatment strategies. The accumulated evidence suggests that a continued focus primarily on individual-level contributors will be suboptimal in promoting weight management at the population level. Here, we consider individual biological and physiological processes within the broader context of sociodemographic and sociocultural exposures as well as environmental changes to optimize research priorities and public health efforts. This requires a consideration of a systems-level approach that efficiently addresses both systemic and group-specific environmental determinants, including psychosocial factors, that often serve as a barrier to otherwise efficacious prevention and treatment options. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota. Our findings suggested that quinoa yogurt could significantly reduce the body weight gain and fat tissue weight of high-fat diet (HFD)-fed obese mice. In addition, quinoa yogurt significantly reduced liver steatosis and enhanced glucose homeostasis and insulin sensitivity. Additional research indicates that quinoa yogurt can reduce the levels of proinflammatory cytokines (i.e., tumor necrosis factor α, IL-1β, and IL-6) and inhibit endotoxemia and systemic inflammation. The characteristics of the gut microbiota were then determined by analyzing 16S rRNA. In addition, we discovered that the gut microbiota was disturbed by HFD consumption. Particularly, intestinal probiotics and beneficial intestinal secretions were increased, leading to the expression of glucagon-like peptide-1 in the colon, contributing to NAFLD. Furthermore, endotoxemia and systemic inflammation in HFD-fed mice were restored to the level of control mice when they were fed yogurt and quinoa. Therefore, yogurt containing quinoa can effectively alleviate NAFLD symptoms and may exert its effects via microbiome-gut-liver axis mechanisms. According to some research, the role of the enteric-liver axis may also influence metabolic disorders to reduce the development of NAFLD.

The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. The gut-liver axis contributes to NASH, but the mechanisms involved and the consequences for NASH-induced fibrosis and liver cancer remain unknown. We investigated the role of gastrointestinal B cells in the development of NASH, fibrosis and NASH-induced HCC.

C57BL/6J wild-type (WT), B cell-deficient and different immunoglobulin-deficient or transgenic mice were fed distinct NASH-inducing diets or standard chow for 6 or 12 months, whereafter NASH, fibrosis, and NASH-induced HCC were assessed and analysed. Specific pathogen-free/germ-free WT and μMT mice (containing B cells only in the gastrointestinal tract) were fed a choline-deficient high-fat diet, and treated with an anti-CD20 antibody, whereafter NASH and fibrosis were assessed. Tissue biopsy samples from patients with simple steatosis, NASH and cirrhosis were analysed to correlate the secretion of immunoglobulins to clinicopathological features. Flow cytometry, immunohistochemistry and single-cell RNA-sequencing analysis were performed in liver and gastrointestinal tissue to characterise immune cells in mice and humans.

Activated intestinal B cells were increased in mouse and human NASH samples and licensed metabolic T-cell activation to induce NASH independently of antigen specificity and gut microbiota. Genetic or therapeutic depletion of systemic or gastrointestinal B cells prevented or reverted NASH and liver fibrosis. IgA secretion was necessary for fibrosis induction by activating CD11b+CCR2+F4/80+CD11c-FCGR1+ hepatic myeloid cells through an IgA-FcR signalling axis. Similarly, patients with NASH had increased numbers of activated intestinal B cells; additionally, we observed a positive correlation between IgA levels and activated FcRg+ hepatic myeloid cells, as well the extent of liver fibrosis.

Intestinal B cells and the IgA-FcR signalling axis represent potential therapeutic targets for the treatment of NASH.

There is currently no effective treatment for non-alcoholic steatohepatitis (NASH), which is associated with a substantial healthcare burden and is a growing risk factor for hepatocellular carcinoma (HCC). We have previously shown that NASH is an auto-aggressive condition aggravated, amongst others, by T cells. Therefore, we hypothesized that B cells might have a role in disease induction and progression. Our present work highlights that B cells have a dual role in NASH pathogenesis, being implicated in the activation of auto-aggressive T cells and the development of fibrosis via activation of monocyte-derived macrophages by secreted immunoglobulins (e.g., IgA). Furthermore, we show that the absence of B cells prevented HCC development. B cell-intrinsic signalling pathways, secreted immunoglobulins, and interactions of B cells with other immune cells are potential targets for combinatorial NASH therapies against inflammation and fibrosis.

Approximately 400 million people work and live in high-altitude areas and suffer from memory dysfunction worldwide. Until now, the role of the intestinal flora in plateau-induced brain damage has rarely been reported. To address this, we investigated the effect of intestinal flora on spatial memory impairment induced by high altitudes based on the microbiome-gut-brain axis theory. C57BL/6 mice were divided into three groups: control, high-altitude (HA), and high-altitude antibiotic treatment (HAA) group. The HA and HAA groups were exposed to a low-pressure oxygen chamber that simulated an altitude of 4000 m above sea level (m. a. s.l.) for 14 days, with the air pressure in the chamber set at 60-65 kPa. The results showed that spatial memory dysfunction induced by the high-altitude environment was aggravated by antibiotic treatment, manifesting as lowered escape latency and hippocampal memory-related proteins (BDNF and PSD-95). 16 S rRNA sequencing showed a remarkable separation of the ileal microbiota among the three groups. Antibiotic treatment exacerbated the reduced richness and diversity of the ileal microbiota in mice in the HA group. Lactobacillaceae were the main target bacteria and were significantly reduced in the HA group, which was exacerbated by antibiotic treatment. Meanwhile, reduced intestinal permeability and ileal immune function in mice exposed high-altitude environment was also aggravated by antibiotic treatment, as indicated by the lowered tight junction proteins and IL-1β and IFN-γ levels. Furthermore, indicator species analysis and Netshift co-analysis revealed that Lactobacillaceae (ASV11) and Corynebacteriaceae (ASV78, ASV25, and ASV47) play important roles in high-altitude exposure-induced memory dysfunction. Interestingly, ASV78 was negatively correlated with IL-1β and IFN-γ levels, indicating that ASV78 may be induced by reduced ileal immune function, which mediates high-altitude environment exposure-induced memory dysfunction. This study provides evidence that the intestinal flora is effective in preventing brain dysfunction caused by exposure to high-altitude environments, suggesting a relationship between the microbiome-gut-brain axis and altitude exposure.

Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.

The gut microbiota impacts systemic levels of multiple metabolites including NAD⁺ precursors through diverse pathways. Nicotinamide riboside (NR) is an NAD⁺ precursor capable of regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter, PnuC. We hypothesized that dietary NR supplementation would modify the gut microbiota across intestinal sections. We determined the effects of 12 weeks of NR supplementation on the microbiota composition of intestinal segments of high-fat diet-fed (HFD) rats. We also explored the effects of 12 weeks of NR supplementation on the gut microbiota in humans and mice. In rats, NR reduced fat mass and tended to decrease body weight. Interestingly, NR increased fat and energy absorption but only in HFD-fed rats. Moreover, 16S rRNA gene sequencing analysis of intestinal and fecal samples revealed an increased abundance of species within Erysipelotrichaceae and Ruminococcaceae families in response to NR. PnuC-positive bacterial strains within these families showed an increased growth rate when supplemented with NR. The abundance of species within the Lachnospiraceae family decreased in response to HFD irrespective of NR. Alpha and beta diversity and bacterial composition of the human fecal microbiota were unaltered by NR, but in mice, the fecal abundance of species within Lachnospiraceae increased while abundances of Parasutterella and Bacteroides dorei species decreased in response to NR. In conclusion, oral NR altered the gut microbiota in rats and mice, but not in humans. In addition, NR attenuated body fat mass gain in rats, and increased fat and energy absorption in the HFD context.

A 90-day experiment was conducted to explore the effects of creatine on growth performance, liver health status, metabolites, and gut microbiota in Megalobrama amblycephala. There were 6 treatments as follows: control (CD, 29.41% carbohydrates), high carbohydrate (HCD, 38.14% carbohydrates), betaine (BET, 1.2% betaine + 39.76% carbohydrates), creatine 1 (CRE1, 0.5% creatine + 1.2% betaine + 39.29% carbohydrates), creatine 2 (CRE2, 1% creatine + 1.2% betaine + 39.50% carbohydrates), and creatine 3 (CRE3, 2% creatine + 1.2% betaine + 39.44% carbohydrates). The results showed that supplementing creatine and betaine together reduced the feed conversion ratio significantly (P < 0.05, compared to CD and HCD) and improved liver health (compared to HCD). Compared with the BET group, dietary creatine significantly increased the abundances of Firmicutes, Bacteroidota, ZOR0006, and Bacteroides and decreased the abundances of Proteobacteria, Fusobacteriota, Vibrio, Crenobacter, and Shewanella in the CRE1 group. Dietary creatine increased the content of taurine, arginine, ornithine, γ-aminobutyric acid (g-ABA), and creatine (CRE1 vs. BET group) and the expression of creatine kinase (ck), sulfinoalanine decarboxylase (csad), guanidinoacetate N-methyltransferase (gamt), glycine amidinotransferase (gatm), agmatinase (agmat), diamine oxidase1 (aoc1), and glutamate decarboxylase (gad) in the CRE1 group. Overall, these results suggested that dietary supplementation of creatine (0.5-2%) did not affect the growth performance, but it altered the gut microbial composition at the phylum and genus levels, which might be beneficial to the gut health of M. amblycephala; dietary creatine also increased the serum content of taurine by enhancing the expressions of ck and csad and increased the serum content of g-ABA by enhancing the arginine content and the expressions of gatm, agmat, gad, and aoc1.

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabetic subjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

Gut microbiota regulates essential processes of host metabolism and physiology: synthesis of vitamins, digestion of foods non-digestible by the host (such as fibers), and-most important-protects the digestive tract from pathogens. In this study, we focus on the CRISPR/Cas9 technology, which is extensively used to correct multiple diseases, including liver diseases. Then, we discuss the non-alcoholic fatty liver disease (NAFLD), affecting more than 25% of the global population; colorectal cancer (CRC) is second in mortality. We give space to rarely discussed topics, such as pathobionts and multiple mutations. Pathobionts help to understand the origin and complexity of the microbiota. Since several types of cancers have as target the gut, it is vital extending the research of multiple mutations to the type of cancers affecting the gut-liver axis.

This study aims to investigate the long-term effects of spirulina supplementation in a high-fat diet (HFD) on rumen morphology, rumen fermentation, and the composition of rumen microbiota in lambs. Spirulina is a blue-green microalgae that has been shown to have high nutritional value for livestock.

Fifty-four lambs were randomly divided into three groups: a normal chow diet (NCD) group, a high-fat diet (HFD) group, and a high-fat diet supplemented with 3% spirulina (HFD+S) group. Rumen morphology, rumen fermentation, and rumen microbiota were analyzed at the end of the study.

Spirulina supplementation improved the concentration of volatile fatty acids and rumen papilla length. Additionally, there was a tendency for an increase in rumen weight and an upregulation of the genes Claudin-1, Claudin-4, and Occludin in the HFD+S group. Pyrosequencing of the 16S ribosomal RNA gene also showed that spirulina supplementation significantly changed the rumen microbiota composition in the HFD group, with a decrease in richness and diversity. Specifically, the relative abundance of Prevotella 9 and Megasphaera was significantly increased in the HFD group compared to the NCD group, while spirulina supplementation reversed these changes.

This study suggests that 3% spirulina supplementation can improve rumen development and fermentation, and effectively relieve rumen microbe disorders in lambs caused by a high-fat diet. However, further research is needed to confirm the findings and to examine the long-term effects of spirulina supplementation in different types of livestock and under different dietary conditions.

Although short-term feeding studies demonstrated effects of grains, fiber, and gluten on gut microbiome composition, the impact of habitual intake of these dietary factors is poorly understood. We examined whether habitual intakes of whole and refined grains, fiber, and gluten are associated with gut microbiota in a cross-sectional study. This study included 779 participants from the multi-ethnic Food and Microbiome Longitudinal Investigation study. Bacterial 16SV4 rRNA gene from baseline stool was amplified and sequenced using Illumina MiSeq. Read clustering and taxonomic assignment was performed using QIIME2. Usual dietary intake was assessed by a 137-item food frequency questionnaire. Association of diet with gut microbiota was assessed with respect to overall composition and specific taxon abundances. Whole grain intake was associated with overall composition, as measured by the Jensen-Shannon divergence (multivariable-adjusted P trend for quartiles = 0.03). The highest intake quartile was associated with higher abundance of Bacteroides plebeius, Faecalibacterium prausnitzii, Blautia producta, and Erysipelotrichaceae and lower abundance of Bacteroides uniformis. These bacteria also varied by dietary fiber intake. Higher refined grain and gluten intake was associated with lower Shannon diversity (P trend < 0.05). These findings suggest that whole grain and dietary fiber are associated with overall gut microbiome structure, largely fiber-fermenting microbiota. Higher refined grain and gluten intakes may be associated with lower microbial diversity.

Regular consumption of whole grains and dietary fiber was associated with greater abundance of gut bacteria that may lower risk of colorectal cancer. Further research on the association of refined grains and gluten with gut microbial composition is needed to understand their roles in health and disease.

At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.

Growing evidence suggests that there is an essential link between the gut and lungs. Asthma is a common chronic inflammatory disease and is considered a heterogeneous disease. While it has been documented that eosinophilic asthma affects gut immunity and the microbiome, the effect of other types of asthma on the gut environment has not been examined. In this study, we utilized an OVA/poly I:C-induced mixed granulocytic asthma model and found increased Tregs without significant changes in other inflammatory cells in the colon. Interestingly, an altered gut microbiome has been observed in a mixed granulocytic asthma model. We observed an increase in the relative abundance of the Faecalibaculum genus and Erysipelotrichaceae family, with a concomitant decrease in the relative abundance of the genera Candidatus arthromitus and Streptococcus. The altered gut microbiome leads to changes in the abundance of genes associated with microbial metabolism, such as glycolysis. We found that mixed granulocytic asthma mainly affects the gut microbial composition and metabolism, which may have important implications in the severity and development of asthma and gut immune homeostasis. This suggests that altered gut microbial metabolism may be a potential therapeutic target for patients with mixed granulocytic asthma.