Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals

Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.     

The Microbiota and Microbiome in Aging: Potential Implications in Health and Age‐Related Diseases

Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm‐aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long‐term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.     

Microbiome changes associated with acute and chronic pancreatitis: A systematic review

BackgroundAltered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with acute (AP) and chronic pancreatitis (CP), or whether these disease states alter the environment to enable pathogenic microbial composition changes to occur. We undertook a systematic review to characterize the gut microbiome in pancreatitis patients.MethodsMEDLINE and EMBASE were searched for studies on microbiota in pancreatitis published from January 1, 2000 to June 5, 2020. Animal studies, reviews, case reports, and non-English articles were excluded. A frequency analysis was performed for outcomes reported in ≥2 studies and studies were analyzed for risk of bias and quality of evidence.Results22 papers met inclusion criteria; 15 included AP, 7 included CP. No studies were appropriately designed to assess whether alterations in the gut microbiome exacerbate pancreatitis or develop as a result of pancreatitis. We did identify several patterns of microbiome changes that are associated with pancreatitis. The gut microbiome demonstrated decreased alpha diversity in 3/3 A P studies and 3/3 C P studies. Beta diversity analysis revealed differences in bacterial community composition in the gut microbiome in 2/2 A P studies and 3/3 C P studies. Functionally, gut microbiome changes were associated with infectious pathways in AP and CP. Several studies suffered from high risk of bias and inadequate quality.ConclusionsDetecting differences in microbial composition associated with AP and CP may represent a diagnostic tool. Appropriately controlled longitudinal studies are needed to determine whether microbiome changes are causative or reactive in pancreatitis.     

Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes

ABSTRACT

Type 2 diabetes (T2D) is associated with reduced gut microbiome diversity, although the cause is unclear. Metabolites generated by gut microbes also appear to be causative factors in T2D. We therefore searched for serum metabolites predictive of gut microbiome diversity in 1018 females from TwinsUK with concurrent metabolomic profiling and microbiome composition. We generated a Microbial Metabolites Diversity (MMD) score of six circulating metabolites that explained over 18% of the variance in microbiome alpha diversity. Moreover, the MMD score was associated with a significantly lower odds of prevalent (OR[95%CI] = 0.22[0.07;0.70], P = .01) and incident T2D (HR[95%CI] = 0.31[0.11,0.90], P = .03). We replicated our results in 1522 individuals from the ARIC study (prevalent T2D: OR[95%CI] = 0.79[0.64,0.96], P = .02, incident T2D: HR[95%CI] = 0.87[0.79,0.95], P = .003). The MMD score mediated 28%[15%,94%] of the total effect of gut microbiome on T2D after adjusting for confounders. Metabolites predicting higher microbiome diversity included 3-phenylpropionate(hydrocinnamate), indolepropionate, cinnamoylglycine and 5-alpha-pregnan-3beta,20 alpha-diol monosulfate(2) of which indolepropionate and phenylpropionate have already been linked to lower incidence of T2D. Metabolites correlating with lower microbial diversity included glutarate and imidazole propionate, of which the latter has been implicated in insulin resistance. Our results suggest that the effect of gut microbiome diversity on T2D is largely mediated by microbial metabolites, which might be modifiable by diet.     

Indonesian children fecal microbiome from birth until weaning was different from microbiomes of their mothers

ABSTRACT

Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainly Bacteroides and Bifidobacterium, which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of the Prevotella type, with decreasing levels of Bifidobacterium, thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning. The fecal Bifidobacterium in children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor.     

Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children

Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.     

A Comparison of Two Single‐Item Screeners for Hazardous Drinking and Alcohol Use Disorder

Background: There is increasing interest in and physician support for the use of single‐item screeners for problem drinking. Methods: In a representative sample of U.S. adults (n = 43,093) and within selected subgroups, past‐year frequency of drinking 5+/4+ drinks and maximum drinks consumed on any day were evaluated as screeners for past‐year alcohol dependence, any alcohol use disorder (AUD), and any AUD or hazardous drinking, using standard measures of screening performance. AUDs were defined according to DSM‐IV criteria. Hazardous drinking was defined as consuming >14 drinks/wk or 5+ drinks on any day for men and >7 drinks/wk or 4+ drinks on any day for women. Results: Optimal cutpoints for both screeners varied across population subgroups, and these variations should be taken into account in order to maximize screening performance. At the optimal cutpoints for the total population, the sensitivity and specificity of maximum drinks were 89% and 82% for dependence at ≥5 drinks, 90% and 79% for any AUD at ≥4 drinks, and 90% and 96% for any AUD or hazardous drinking at ≥4 drinks. Comparable values of sensitivity and specificity for 5+/4+ frequency were 90% and 83% at ≥3 times a year, 87% and 82% at ≥once a year, and 88% and 100% at ≥once a year, respectively. Specificity was lower when only past‐year drinkers were considered. The 5+/4+ frequency screener yielded fairly low sensitivity in predicting alcohol problems among the elderly and among Blacks. Results supported a past‐year reference period for frequency of 5+/4+ drinks and substantiated gender‐ and age‐specific thresholds for defining risk drinking. Conclusions: Both of the single‐item screeners performed nearly on a par with the AUDIT‐C and have potential for use in primary and emergency care settings.     

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and ‘dysbiosis’ is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non‐IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High‐quality studies have shown that VSL#3 (a high‐potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.     

Lifetime alcohol intake and pattern of alcohol consumption in patients with alcohol-induced pancreatitis in comparison with patients with alcohol use disorder

Objective: To examine lifetime drinking patterns in men and women with alcohol-induced pancreatitis (AIP) in comparison with patients with alcoholic use disorder (AUD) without pancreatic disease.

Methods: Alcohol consumption patterns were assessed using a validated questionnaire, the Lifetime Drinking History (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for gender and age (+/? 5 years) with patients with AUD in addiction treatment.

Results: A total of 45 patients with AIP (35 males, 10 females) and 45 AUD patients were included. Alcohol consumption patterns were not significantly different between males and females with AIP and those with history of acute AIP and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD patients were similar in terms of onset age and duration of alcohol consumption, lifetime alcohol intake and drinks per drinking day. A higher proportion of binge drinking was found among patients with AUD than those with AIP (median 1.00 vs. 0.94, p?=?.01). Males with AUD had lower onset age (15 vs. 16 years, p?=?.03), higher total amount of spirits (35520 vs. 10450 drinks, p?=?.04) and higher proportion of binge drinking (1.00 vs. 0.97, p?=?.01) than males with AIP, whereas females with AIP and AUD had similar drinking patterns.

Conclusions: Alcohol drinking patterns and lifetime drinking history was similar in patients with AIP and patients with AUD. Males with AIP had lower total amount of spirits and lower proportion of binge drinking than those with AUD, suggesting the idiosyncratic etiology of AIP.     

Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice

Shifts in microbial populations of the intestinal tract have been associated with a multitude of nutritional, autoimmune, and infectious diseases. The limited diversity following antibiotic treatments creates a window for opportunistic pathogens, diarrhea, and inflammation as the microbiome repopulates. Depending on the antibiotics used, microbial diversity can take weeks to months to recover. To alleviate this loss of diversity in the intestinal microbiota, supplementation with probiotics has become increasingly popular. However, our understanding of the purported health benefits of these probiotic bacteria and their ability to shape the microbiome is significantly lacking. This study examined the impact of probiotics concurrent with antibiotic treatment or during the recovery phase following antibiotic treatment of mice. We found that probiotics did not appear to colonize the intestine themselves or shift the overall diversity of the intestinal microbiota. However, the probiotic supplementation did significantly change the types of bacteria which were present. In particular, during the recovery phase the probiotic caused a suppression of Enterobacteriaceae outgrowth (Shigella and Escherichia) while promoting a blooming of Firmicutes, particularly from the Anaerotruncus genus. These results indicate that probiotics have a significant capacity to remodel the microbiome of an individual recovering from antibiotic therapy.     

Exercise influence on the microbiome–gut–brain axis

ABSTRACT

The microbiome in the gut is a diverse environment, housing the majority of our bacterial microbes. This microecosystem has a symbiotic relationship with the surrounding multicellular organism, and a balance and diversity of specific phyla of bacteria support general health. When gut bacteria diversity diminishes, there are systemic consequences, such as gastrointestinal and psychological distress. This pathway of communication is known as the microbiome–gut–brain axis. Interventions such as probiotic supplementation that influence microbiome also improve both gut and brain disorders. Recent evidence suggests that aerobic exercise improves the diversity and abundance of genera from the Firmcutes phylum, which may be the link between the positive effects of exercise on the gut and brain. The purpose of this review is to explain the complex communication pathway of the microbiome–gut–brain axis and further examine the role of exercise on influencing this communication highway.     

The gut microbial influence on cholestatic liver disease

Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.     

Characterization of the human gut microbiome during travelers' diarrhea

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.     

Lifetime drinking history in patients with alcoholic liver disease and patients with alcohol use disorder without liver disease

Objective: To determine the differences in lifetime alcohol intake (LAI) and drinking patterns between patients with alcoholic liver disease (ALD) and alcohol use disorder (AUD) without notable liver injury and between males and females with ALD.

Methods: Alcohol drinking patterns were assessed using the Lifetime Drinking History (LDH) a validated questionnaire, during an outpatient visit. Patients with AUD, currently in addiction treatment, were matched for gender and age (±5 years) with the ALD group.

Results: A total of 39 patients with ALD (26 males and 13 females; median age 58) and equal number of AUD patients were included (median age 56 years). The onset age for alcohol drinking and duration of alcohol consumption was similar in ALD and AUD. The number of drinking days was higher in women with ALD than in women with AUD: 4075 [(3224–6504) versus 2092 (1296–3661), p?=?.0253]. The LAI and drinks per drinking day (DDD) were not significantly different between patients with ALD and AUD. Females with ALD had lower LAI than males with ALD: 32,934 (3224–6504) versus 50,923 (30,360–82,195), p?=?.0385, fewer DDD (p?=?.0112), and lower proportion of binge drinking as compared to males with ALD (p?=?.0274).

Conclusions: The total LAI was similar in patients with ALD and AUD. The number of drinking days over the lifetime was associated with the development of ALD in females. Females with ALD had significantly lower alcohol consumption than men with ALD despite similar duration in years of alcohol intake which supports the concept of female propensity of ALD.     

Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother's periconceptional diet

Shifts in the maternal gut microbiome have been implicated in metabolic adaptations to pregnancy. We investigated how pregnancy and diet interact to influence the composition of the maternal gut microbiota. Female C57BL/6 mice were fed either a control or a high fat diet for 8 weeks prior to mating. After confirmation of pregnancy, maternal weight gain and food intake were recorded. Fecal pellets were collected at 2 timepoints prior to mating (at the beginning of the experiment, and after 6 weeks of the specified diet) and at 4 timepoints during pregnancy (gestation day 0.5, 5.5, 10.5, and 15.5). The microbial composition and predicted metabolic functionality of the non-pregnant and pregnant gut was determined via sequencing of the variable 3 region of the 16S rRNA gene. Upon conception, differences in gut microbial communities were observed in both control and high fat-fed mice, including an increase in mucin-degrading bacteria. Control versus high fat-fed pregnant mice possessed the most profound changes to their maternal gut microbiota as indicated by statistically significant taxonomic differences. High fat-fed pregnant mice, when compared to control-fed animals, were found to be significantly enriched in microbes involved in metabolic pathways favoring fatty acid, ketone, vitamin, and bile synthesis. We show that pregnancy-induced changes in the female gut microbiota occur immediately at the onset of pregnancy, are vulnerable to modulation by diet, but are not dependent upon increases in maternal weight gain during pregnancy. High fat diet intake before and during pregnancy results in distinctive shifts in the pregnant gut microbiota in a gestational-age dependent manner and these shifts predict significant differences in the abundance of genes that favor lipid metabolism, glycolysis and gluconeogenic metabolic pathways over the course of pregnancy.     

Alternations of gut microbiota composition in neonates conceived by assisted reproductive technology and its relation to infant growth

ABSTRACT

The gut microbiome in newborns may be strongly influenced by their intrinsic host microenvironmental factors (e.g., the gestational age) and has been linked to their short-term growth and potentially future health. It is yet unclear whether early microbiota composition is significantly different in newborns conceived by assisted reproductive technology (ART) when compared with those who were conceived spontaneously. Additionally, little is known about the effect of gut microbiota composition on weight gain in early infancy. We aimed to characterize the features and the determinants of the gut microbiome in ART newborns and to assess the impact of early microbiota composition on their weight gain in early infancy in mother-infant dyads enrolled in the China National Birth Cohort (CNBC). Among 118 neonates born by ART and 91 neonates born following spontaneous conception, we observed significantly reduced gut microbiota α-diversity and declined Bacteroidetes relative abundance in ART neonates. The microbiota composition of ART neonates was largely driven by specific ART treatments, hinting the importance of fetus intrinsic host microenvironment on the early microbial colonization. Following up these neonates for six months after their births, we observed the effects of gut microbiome composition on infant rapid weight gaining. Collectively, we identified features and determinants of the gut microbiota composition in ART neonates, and provided evidence for the importance of microbiota composition in neonatal growth.     

Probiotics drive gut microbiome triggering emotional brain signatures

ABSTRACT

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks’ probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.     

Gut microbiota and irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.