Obesity is a disease characterized by the excessive accumulation of fat at several body sites. Fat deposits around the waist are particularly detrimental and are associated with the onset of other pathologies such as cardiovascular disease and type 2 diabetes (T2D) (1). A body mass index (BMI) of 40 or higher is classified as severe obesity (2). In addition to the metabolic alterations inherent to obesity, patients often experience mobility problems and everyday life is severely affected. In most cases, dietary and exercise interventions have limited impact on weight loss; therefore, other approaches, such as bariatric surgery, are employed (3). Although different types of bariatric surgery exist, the use of malabsorptive bariatric surgery has demonstrated particularly favorable outcomes in obese patients. The most common procedure is Roux-en-Y gastric bypass (RYGB) although one-anastomosis gastric bypass (OAGB) has also been used successfully. Both surgeries involve rearranging the intestines in a way that limits nutrients absorption by bypassing the proximal portion of the small intestine and facilitating the passage of poorly digested food to the distal small intestine and colon (1, 4). These changes contribute to modifications in gut bacterial diversity and balance. This new microbial equilibrium influences the capacity of the gut bacteria to perform biologically relevant functions, including the synthesis of essential vitamins, the production of signaling molecules and digestion of nutrients (5).

Prebiotics and probiotics have been utilized to modulate the abundance of gut bacteria in the host. For example, fiber intake has been widely recommended to promote the growth of short-chain fatty acid (SCFA)-producing bacteria (6). However, the benefits of specific bacteria should be evaluated in a context-dependent manner since some bacteria such as the SCFA-producing bacteria Coprococcus has been linked to both positive and negative traits (7–16). Although less is known about the role of other dietary micronutrients in shaping the gut flora, evidence suggests that vitamins, minerals and trace elements in the diet can alter gut bacteria composition leading to improvements of clinical variables (17, 18). Particularly, thiamin and magnesium have been linked to changes in the abundance of Bacteroides, Alistipes, Bacilli and Bifidobacterium as well as to improvements in blood glucose, medium-chain fatty acids and some metabolic syndrome parameters (17, 19, 20).

In this study, we identified a species of Coprococcus whose abundance was higher in patients with greater BMI after bariatric surgery. The response of Coprococcus sp. to dietary intake was subsequently investigated, and we identified two micronutrients (magnesium and thiamin) that correlated with its abundance in the gut. Given the essential role of micronutrients in microbiota composition and the altered nutrient absorption following bariatric surgery, understanding the nutrients-microbiota relationship is critical for post-operative dietary guidance. Changes in several other bacterial taxa and associated metabolic pathways were observed in patients who underwent malabsorptive bariatric surgery.

Bariatric surgery is a procedure that has been shown to substantially reduce weight and improve metabolic alterations associated with diabetes. Major remodeling of the digestive tract contributes to these changes by increasing the release of anorexigenic hormones and decreasing nutrient absorption but also by altering the gut microbiota composition (32). Indeed, our study revealed that bacterial diversity (alpha and beta) varied greatly after bariatric surgery with several species decreasing in abundance. The abundance of one of these bacteria (g_Coprococcus;s_ according to QIIME2 taxonomic assignation but referred as Coprococcus sp.) showed an opposite relationship with BMI before and after surgery and was positively correlated with magnesium and thiamin intake in the post-surgery group.

The results of this study are consistent with previously published findings showing that bariatric surgery improves patients´ health. Patients in the present study lost an average of 24% of their initial weight and they were reclassified from class III obesity to class I obesity. At baseline, 71.4% of the patients were taking some type of hypoglycemic medication, but this proportion was reduced to 14.3% after surgery. Biochemical variables such as fasting glucose, triglycerides, LDL and total cholesterol improved as well (Table 1).

Improvement in anthropometric and biochemical parameters was accompanied by a decrease in Shannon and Simpson diversity indices (Figure 1). This reduction in diversity is attributed to the extensive remodeling of the gut, which prevents the transit of food through the first portion of the small intestine, leading to incomplete digestion and overall changes in the gut microenvironment. Beta diversity estimated by Bray–Curtis, unweighted and weighted UniFrac indices showed clear differences between the compared groups (Figure 1). These results indicate that the bacterial composition is strongly modified after malabsorptive bariatric surgery. At the phylum level, the abundance of Firmicutes decreased, while that of Bacteroidetes and Fusobacteria increased (Supplementary Material S1). These findings are consistent with reports in the literature indicating that the microbiota of obese patients is enriched in Firmicutes (33). At lower taxonomic levels and after adjusting the p value by false discovery rate, we identified 18 taxa that varied in abundance (Figure 3). Most taxa decreased in abundance after bariatric surgery (14 out of 18). Taxa that decreased in abundance belonged to the order Clostridiales and the families Lachnospiraceae and Ruminococcaceae. The genomes of members of both families are known to contain ATP-binding cassette (ABC) genes and other genes encoding enzymes that participate starch and sugars degradation. Hydrolysis of these sugars results in the production of SCFAs (butyrate, acetate, and propionate) (34). Although increased SCFA production is generally considered beneficial for gut homeostasis, when combined with a greater bacterial capacity to extract energy from the diet, it may contribute to the obese phenotype. In line with this interpretation, we identified enrichment of several pathways involved in starch and sugar degradation (i.e. xylose, galactose, N-acetylmannosamine, N-acetylneuraminate, N-acetylglucosamine, mannan, glucose, rhamnose, fucose, and sucrose) in obese patients (Figure 4).

Another pathway that was enriched in the pre-surgery group was related to the acetylene degradation. The end product of this pathway is microbiota-derived acetate. Evidence indicating that acetate production by the microbiota due to high fructose consumption (which is relatively common in obese patients) leads to activation of hepatic ACSS2 enzyme which transforms acetate to lipogenic acetyl-CoA (35). This occurs in addition to the conversion of glucose and fructose to fatty acids in the liver (36). Thus, increased acetate and lipogenic acetyl-CoA production combined with high-caloric diets in obese pre-surgery patients may contribute to the maintenance of the obese phenotype.

Microbial glycogen degradation and glycogen biosynthesis pathways were enriched in the pre-surgery group as well. The enrichment of both energy-related pathways indicates that the microbiota of severely obese patients has the capacity to manage the energy surplus obtained due to the patients’ intake of high-caloric diets.

Previous reports indicate that approximately 27% of patients undergoing bariatric surgery have thiamin deficiency (37). This is clinically relevant because these patients require lifelong vitamin B1 (thiamin) supplementation. Thiamin is crucial and indirectly involved in the electron transport chain and extraction of energy from carbohydrates but also is required for bacterial growth (38). This essential vitamin is obtained from the diet and as a product of bacterial metabolism. However, not all bacteria have the genes necessary for its de novo synthesis (39). In this study, we found that the abundance of three bacteria (Faecalibacterium prausnitzii, Gemmigers formicilis and Ruminococcus) that require thiamine for their survival but cannot produce thiamine by themselves decreased (Figure 3). These bacteria belong to the Ruminococcaceae family (39). This abundance decrease corresponds to a reduction of the thiazole biosynthesis pathway after the surgery (Figure 4).

Although thiamin is required for normal physiological processes, our results suggest that fine tuning of thiamin intake is desirable in post-surgery patients. We observed that thiamin intake was positively correlated with Coprococcus sp. abundance which in turn was related to higher BMI after surgery (Figures 2b, c). We further observed that the Coprococcus sp. relative abundance in the post-surgery group was positively correlated with magnesium intake (Figure 2a) which is required for the proper activation of vitamin B1 (20, 40). The above-mentioned evidence suggest that thiamin and magnesium intake must be such that it does not have a detrimental effect on BMI mediated by Coprococcus sp. According to the recommended dietary allowance (RDA), 1.1 - 1.2 mg of thiamin and 320–420 mg of magnesium intake are required to maintain normal physiological processes (41, 42). These RDAs values fall near the midpoint of the range of micronutrient intakes quantified from the dietary recall questionnaires of post-surgery patients (Figures 3a, b). Thus, patients whose intake exceeds the RDA may benefit from reducing their daily thiamin and magnesium intake to levels that are closer to the RDA. Future well-controlled studies to explore the feasibility of diet-driven modulation of the Coprococcus sp. abundance in order to enhance weight loss and augment the metabolic benefits of bariatric surgery are needed. In addition, a better understanding of thiamin consumption and/or production by the Coprococcus sp. is necessary as a study by Soto-Martin et al. (43) reported that not all Coprococcus spp. have either the presence of the genetic repertoire for de novo thiamin biosynthesis or show the same growth rate in thiamin-depleted medium. Isolation of Coprococcus sp. from post-bariatric surgery samples followed by in vitro and in silico analysis of its capacity to produce or use thiamin as well as whole-genome sequencing are necessary to clarify the identified positive thiamin-Coprococcus sp.-BMI association.

Interestingly, a negative relationship between Coprococcus sp. abundance and BMI was observed in obese patients before the bariatric surgery (Figure 2d). This is in contrast to the positive relationship found in post-surgery patients. Lozano et al. (44) provided insight into a possible mechanism underlying this opposite relationship. They reported a positive association between high inflammatory index diets and ectopic fat accumulation, but only in patients with lower gut Coprococcus abundance. Obese individuals typically consume high-inflammatory-index diets with high caloric content. Thus, obese patients in this study with lower Coprococuss sp. abundance may be more prone to accumulate ectopic fat and to have a higher BMI. Post-surgery patients follow less inflammatory diets which indicates that this mechanism does not affect them. However, other mechanisms may play a role as determinants of weight loss. For instance, Coprococcuss spp. are SCFA producers with the capacity to extract energy from otherwise undigested diet components (43). Therefore, in the altered post-surgical gut environment, greater Coprococcus sp. abundance combined with a less diverse microbiota and high metabolic efficiency for extracting energy from limited substrates would make it more difficult for patients to lose the obese phenotype. No correlation between thiamin/magnesium intake and Coprococcus sp. abundance was found in severely obese individuals.

The role of Coprococcus in health remains a subject of debate. While a large portion of the scientific literature associates this genus with beneficial traits such as improved insulin sensitivity in metabolically healthy obese individuals (7–9), reduced inflammation, enhance anti-inflammatory molecules, mucin production and tight junctions restoration (10, 11), other studies linked it to with small intestine bacterial overgrowth (12), depressive symptoms (13), inflammatory bowel disease (14), liver tumorigenesis (15) and interstitial cystitis (16). The gut microbiota is a diverse and complex community in which bacterial growth is tightly linked to the available resources. Thus, divergent associations with health and disease may result from differences in microenvironments, diseases and bacteria-bacteria interactions. The findings of this study should be interpreted in light of certain limitations. First, although false discovery rate adjustment was applied in multiple comparison hypotheses testing to control for false positives, replication in larger, independent cohorts from diverse geographical locations is needed to strengthen the conclusions. Second, major intestinal rearrangement following bariatric surgery has been reported as the main driver of most of the changes in the gut microbiota profile (45). However, the contribution of other confounders not evaluated in this study such as medication use and lifestyle modifications should not be excluded and warrants further investigation.

Important changes in clinical variables and microbiota were observed after individuals with severe obesity underwent malabsorptive bariatric surgery. Only 20% of patients who used hypoglycemic medication before surgery continued doing so afterwards, while the remaining 80% did not longer required medication to control their glucose levels. This improvement was accompanied by changes in the gut microbiota alpha and beta diversity. After surgery, the gut microbiota was less diverse, with a decrease in the abundance of several bacterial species. These changes in the microbiota profile led to a reduction in the enrichment of metabolic pathways involved in amino acid, thiamin, sugar degradation and acetate production. The abundance of a species of the genus Coprococcus showed opposite relationships with BMI in pre-surgery and post-surgery individuals. Furthermore, its abundance correlated with magnesium and thiamin intake in individuals who underwent a malabsorptive bariatric surgery.